Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer

Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Lu, Jun [verfasserIn] Li, Guangliang He, Kuifeng Jiang, Weiqin Xu, Cong Li, Zhongqi Wang, Haohao Wang, Weibin Wang, Haiyong Teng, Xiaodong Teng, Lisong

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Luteolin cMet-overexpressing Gastric cancer Patient-derived tumor xenografts

Anmerkung:	© Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Journal of translational medicine - London : BioMed Central, 2003, 13(2015), 1 vom: 01. Feb.
Übergeordnetes Werk:	volume:13 ; year:2015 ; number:1 ; day:01 ; month:02

Links:	Volltext

DOI / URN:	10.1186/s12967-015-0398-z

Katalog-ID:	SPR028954777

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520			\|a Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer.
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allfields	10.1186/s12967-015-0398-z doi (DE-627)SPR028954777 (SPR)s12967-015-0398-z-e DE-627 ger DE-627 rakwb eng Lu, Jun verfasserin aut Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. Luteolin (dpeaa)DE-He213 cMet-overexpressing (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Patient-derived tumor xenografts (dpeaa)DE-He213 Li, Guangliang aut He, Kuifeng aut Jiang, Weiqin aut Xu, Cong aut Li, Zhongqi aut Wang, Haohao aut Wang, Weibin aut Wang, Haiyong aut Teng, Xiaodong aut Teng, Lisong aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 13(2015), 1 vom: 01. Feb. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:13 year:2015 number:1 day:01 month:02 https://dx.doi.org/10.1186/s12967-015-0398-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2015 1 01 02
spelling	10.1186/s12967-015-0398-z doi (DE-627)SPR028954777 (SPR)s12967-015-0398-z-e DE-627 ger DE-627 rakwb eng Lu, Jun verfasserin aut Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. Luteolin (dpeaa)DE-He213 cMet-overexpressing (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Patient-derived tumor xenografts (dpeaa)DE-He213 Li, Guangliang aut He, Kuifeng aut Jiang, Weiqin aut Xu, Cong aut Li, Zhongqi aut Wang, Haohao aut Wang, Weibin aut Wang, Haiyong aut Teng, Xiaodong aut Teng, Lisong aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 13(2015), 1 vom: 01. Feb. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:13 year:2015 number:1 day:01 month:02 https://dx.doi.org/10.1186/s12967-015-0398-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2015 1 01 02
allfields_unstemmed	10.1186/s12967-015-0398-z doi (DE-627)SPR028954777 (SPR)s12967-015-0398-z-e DE-627 ger DE-627 rakwb eng Lu, Jun verfasserin aut Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. Luteolin (dpeaa)DE-He213 cMet-overexpressing (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Patient-derived tumor xenografts (dpeaa)DE-He213 Li, Guangliang aut He, Kuifeng aut Jiang, Weiqin aut Xu, Cong aut Li, Zhongqi aut Wang, Haohao aut Wang, Weibin aut Wang, Haiyong aut Teng, Xiaodong aut Teng, Lisong aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 13(2015), 1 vom: 01. Feb. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:13 year:2015 number:1 day:01 month:02 https://dx.doi.org/10.1186/s12967-015-0398-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2015 1 01 02
allfieldsGer	10.1186/s12967-015-0398-z doi (DE-627)SPR028954777 (SPR)s12967-015-0398-z-e DE-627 ger DE-627 rakwb eng Lu, Jun verfasserin aut Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. Luteolin (dpeaa)DE-He213 cMet-overexpressing (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Patient-derived tumor xenografts (dpeaa)DE-He213 Li, Guangliang aut He, Kuifeng aut Jiang, Weiqin aut Xu, Cong aut Li, Zhongqi aut Wang, Haohao aut Wang, Weibin aut Wang, Haiyong aut Teng, Xiaodong aut Teng, Lisong aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 13(2015), 1 vom: 01. Feb. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:13 year:2015 number:1 day:01 month:02 https://dx.doi.org/10.1186/s12967-015-0398-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2015 1 01 02
allfieldsSound	10.1186/s12967-015-0398-z doi (DE-627)SPR028954777 (SPR)s12967-015-0398-z-e DE-627 ger DE-627 rakwb eng Lu, Jun verfasserin aut Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. Luteolin (dpeaa)DE-He213 cMet-overexpressing (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Patient-derived tumor xenografts (dpeaa)DE-He213 Li, Guangliang aut He, Kuifeng aut Jiang, Weiqin aut Xu, Cong aut Li, Zhongqi aut Wang, Haohao aut Wang, Weibin aut Wang, Haiyong aut Teng, Xiaodong aut Teng, Lisong aut Enthalten in Journal of translational medicine London : BioMed Central, 2003 13(2015), 1 vom: 01. Feb. (DE-627)369084136 (DE-600)2118570-0 1479-5876 nnns volume:13 year:2015 number:1 day:01 month:02 https://dx.doi.org/10.1186/s12967-015-0398-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2015 1 01 02
language	English
source	Enthalten in Journal of translational medicine 13(2015), 1 vom: 01. Feb. volume:13 year:2015 number:1 day:01 month:02
sourceStr	Enthalten in Journal of translational medicine 13(2015), 1 vom: 01. Feb. volume:13 year:2015 number:1 day:01 month:02
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Luteolin cMet-overexpressing Gastric cancer Patient-derived tumor xenografts
isfreeaccess_bool	false
container_title	Journal of translational medicine
authorswithroles_txt_mv	Lu, Jun @@aut@@ Li, Guangliang @@aut@@ He, Kuifeng @@aut@@ Jiang, Weiqin @@aut@@ Xu, Cong @@aut@@ Li, Zhongqi @@aut@@ Wang, Haohao @@aut@@ Wang, Weibin @@aut@@ Wang, Haiyong @@aut@@ Teng, Xiaodong @@aut@@ Teng, Lisong @@aut@@
publishDateDaySort_date	2015-02-01T00:00:00Z
hierarchy_top_id	369084136
id	SPR028954777
language_de	englisch
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MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. 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author	Lu, Jun
spellingShingle	Lu, Jun misc Luteolin misc cMet-overexpressing misc Gastric cancer misc Patient-derived tumor xenografts Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer
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topic_title	Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer Luteolin (dpeaa)DE-He213 cMet-overexpressing (dpeaa)DE-He213 Gastric cancer (dpeaa)DE-He213 Patient-derived tumor xenografts (dpeaa)DE-He213
topic	misc Luteolin misc cMet-overexpressing misc Gastric cancer misc Patient-derived tumor xenografts
topic_unstemmed	misc Luteolin misc cMet-overexpressing misc Gastric cancer misc Patient-derived tumor xenografts
topic_browse	misc Luteolin misc cMet-overexpressing misc Gastric cancer misc Patient-derived tumor xenografts
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title	Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer
ctrlnum	(DE-627)SPR028954777 (SPR)s12967-015-0398-z-e
title_full	Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer
author_sort	Lu, Jun
journal	Journal of translational medicine
journalStr	Journal of translational medicine
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author_browse	Lu, Jun Li, Guangliang He, Kuifeng Jiang, Weiqin Xu, Cong Li, Zhongqi Wang, Haohao Wang, Weibin Wang, Haiyong Teng, Xiaodong Teng, Lisong
container_volume	13
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author-letter	Lu, Jun
doi_str_mv	10.1186/s12967-015-0398-z
title_sort	luteolin exerts a marked antitumor effect in cmet-overexpressing patient-derived tumor xenograft models of gastric cancer
title_auth	Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer
abstract	Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background Aberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear. Methods Two cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays. Results Luteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin. Conclusions Our findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer. © Lu et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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title_short	Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer
url	https://dx.doi.org/10.1186/s12967-015-0398-z
remote_bool	true
author2	Li, Guangliang He, Kuifeng Jiang, Weiqin Xu, Cong Li, Zhongqi Wang, Haohao Wang, Weibin Wang, Haiyong Teng, Xiaodong Teng, Lisong
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