mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling
Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mT...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Zhang, Huiyuan [verfasserIn] Dou, Jun [verfasserIn] Yu, Yang [verfasserIn] Zhao, Yanling [verfasserIn] Fan, Yihui [verfasserIn] Cheng, Jin [verfasserIn] Xu, Xin [verfasserIn] Liu, Wei [verfasserIn] Guan, Shan [verfasserIn] Chen, Zhenghu [verfasserIn] shi, Yan [verfasserIn] Patel, Roma [verfasserIn] Vasudevan, Sanjeev A. [verfasserIn] Zage, Peter E. [verfasserIn] Zhang, Hong [verfasserIn] Nuchtern, Jed G. [verfasserIn] Kim, Eugene S. [verfasserIn] Fu, Songbin [verfasserIn] Yang, Jianhua [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Apoptosis - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996, 20(2014), 1 vom: 26. Nov., Seite 50-62 |
|---|---|
| Übergeordnetes Werk: |
volume:20 ; year:2014 ; number:1 ; day:26 ; month:11 ; pages:50-62 |
| Links: |
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| DOI / URN: |
10.1007/s10495-014-1066-0 |
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| Katalog-ID: |
SPR010501606 |
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| 245 | 1 | 0 | |a mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling |
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| 520 | |a Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. | ||
| 650 | 4 | |a Neuroblastoma |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a mTOR inhibitor |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a INK128 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chemotherapy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Drug resistance |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Dou, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yanling |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Yihui |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhenghu |e verfasserin |4 aut | |
| 700 | 1 | |a shi, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Roma |e verfasserin |4 aut | |
| 700 | 1 | |a Vasudevan, Sanjeev A. |e verfasserin |4 aut | |
| 700 | 1 | |a Zage, Peter E. |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Nuchtern, Jed G. |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Eugene S. |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Songbin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jianhua |e verfasserin |4 aut | |
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10.1007/s10495-014-1066-0 doi (DE-627)SPR010501606 (SPR)s10495-014-1066-0-e DE-627 ger DE-627 rakwb eng 570 ASE 44.00 bkl Zhang, Huiyuan verfasserin aut mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. Neuroblastoma (dpeaa)DE-He213 mTOR inhibitor (dpeaa)DE-He213 INK128 (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug resistance (dpeaa)DE-He213 Dou, Jun verfasserin aut Yu, Yang verfasserin aut Zhao, Yanling verfasserin aut Fan, Yihui verfasserin aut Cheng, Jin verfasserin aut Xu, Xin verfasserin aut Liu, Wei verfasserin aut Guan, Shan verfasserin aut Chen, Zhenghu verfasserin aut shi, Yan verfasserin aut Patel, Roma verfasserin aut Vasudevan, Sanjeev A. verfasserin aut Zage, Peter E. verfasserin aut Zhang, Hong verfasserin aut Nuchtern, Jed G. verfasserin aut Kim, Eugene S. verfasserin aut Fu, Songbin verfasserin aut Yang, Jianhua verfasserin aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 20(2014), 1 vom: 26. Nov., Seite 50-62 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:20 year:2014 number:1 day:26 month:11 pages:50-62 https://dx.doi.org/10.1007/s10495-014-1066-0 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE AR 20 2014 1 26 11 50-62 |
| spelling |
10.1007/s10495-014-1066-0 doi (DE-627)SPR010501606 (SPR)s10495-014-1066-0-e DE-627 ger DE-627 rakwb eng 570 ASE 44.00 bkl Zhang, Huiyuan verfasserin aut mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. Neuroblastoma (dpeaa)DE-He213 mTOR inhibitor (dpeaa)DE-He213 INK128 (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug resistance (dpeaa)DE-He213 Dou, Jun verfasserin aut Yu, Yang verfasserin aut Zhao, Yanling verfasserin aut Fan, Yihui verfasserin aut Cheng, Jin verfasserin aut Xu, Xin verfasserin aut Liu, Wei verfasserin aut Guan, Shan verfasserin aut Chen, Zhenghu verfasserin aut shi, Yan verfasserin aut Patel, Roma verfasserin aut Vasudevan, Sanjeev A. verfasserin aut Zage, Peter E. verfasserin aut Zhang, Hong verfasserin aut Nuchtern, Jed G. verfasserin aut Kim, Eugene S. verfasserin aut Fu, Songbin verfasserin aut Yang, Jianhua verfasserin aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 20(2014), 1 vom: 26. Nov., Seite 50-62 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:20 year:2014 number:1 day:26 month:11 pages:50-62 https://dx.doi.org/10.1007/s10495-014-1066-0 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE AR 20 2014 1 26 11 50-62 |
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10.1007/s10495-014-1066-0 doi (DE-627)SPR010501606 (SPR)s10495-014-1066-0-e DE-627 ger DE-627 rakwb eng 570 ASE 44.00 bkl Zhang, Huiyuan verfasserin aut mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. Neuroblastoma (dpeaa)DE-He213 mTOR inhibitor (dpeaa)DE-He213 INK128 (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug resistance (dpeaa)DE-He213 Dou, Jun verfasserin aut Yu, Yang verfasserin aut Zhao, Yanling verfasserin aut Fan, Yihui verfasserin aut Cheng, Jin verfasserin aut Xu, Xin verfasserin aut Liu, Wei verfasserin aut Guan, Shan verfasserin aut Chen, Zhenghu verfasserin aut shi, Yan verfasserin aut Patel, Roma verfasserin aut Vasudevan, Sanjeev A. verfasserin aut Zage, Peter E. verfasserin aut Zhang, Hong verfasserin aut Nuchtern, Jed G. verfasserin aut Kim, Eugene S. verfasserin aut Fu, Songbin verfasserin aut Yang, Jianhua verfasserin aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 20(2014), 1 vom: 26. Nov., Seite 50-62 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:20 year:2014 number:1 day:26 month:11 pages:50-62 https://dx.doi.org/10.1007/s10495-014-1066-0 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE AR 20 2014 1 26 11 50-62 |
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10.1007/s10495-014-1066-0 doi (DE-627)SPR010501606 (SPR)s10495-014-1066-0-e DE-627 ger DE-627 rakwb eng 570 ASE 44.00 bkl Zhang, Huiyuan verfasserin aut mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. Neuroblastoma (dpeaa)DE-He213 mTOR inhibitor (dpeaa)DE-He213 INK128 (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug resistance (dpeaa)DE-He213 Dou, Jun verfasserin aut Yu, Yang verfasserin aut Zhao, Yanling verfasserin aut Fan, Yihui verfasserin aut Cheng, Jin verfasserin aut Xu, Xin verfasserin aut Liu, Wei verfasserin aut Guan, Shan verfasserin aut Chen, Zhenghu verfasserin aut shi, Yan verfasserin aut Patel, Roma verfasserin aut Vasudevan, Sanjeev A. verfasserin aut Zage, Peter E. verfasserin aut Zhang, Hong verfasserin aut Nuchtern, Jed G. verfasserin aut Kim, Eugene S. verfasserin aut Fu, Songbin verfasserin aut Yang, Jianhua verfasserin aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 20(2014), 1 vom: 26. Nov., Seite 50-62 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:20 year:2014 number:1 day:26 month:11 pages:50-62 https://dx.doi.org/10.1007/s10495-014-1066-0 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE AR 20 2014 1 26 11 50-62 |
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10.1007/s10495-014-1066-0 doi (DE-627)SPR010501606 (SPR)s10495-014-1066-0-e DE-627 ger DE-627 rakwb eng 570 ASE 44.00 bkl Zhang, Huiyuan verfasserin aut mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. Neuroblastoma (dpeaa)DE-He213 mTOR inhibitor (dpeaa)DE-He213 INK128 (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug resistance (dpeaa)DE-He213 Dou, Jun verfasserin aut Yu, Yang verfasserin aut Zhao, Yanling verfasserin aut Fan, Yihui verfasserin aut Cheng, Jin verfasserin aut Xu, Xin verfasserin aut Liu, Wei verfasserin aut Guan, Shan verfasserin aut Chen, Zhenghu verfasserin aut shi, Yan verfasserin aut Patel, Roma verfasserin aut Vasudevan, Sanjeev A. verfasserin aut Zage, Peter E. verfasserin aut Zhang, Hong verfasserin aut Nuchtern, Jed G. verfasserin aut Kim, Eugene S. verfasserin aut Fu, Songbin verfasserin aut Yang, Jianhua verfasserin aut Enthalten in Apoptosis Dordrecht [u.a.] : Springer Science + Business Media B.V, 1996 20(2014), 1 vom: 26. Nov., Seite 50-62 (DE-627)306311577 (DE-600)1495863-6 1573-675X nnns volume:20 year:2014 number:1 day:26 month:11 pages:50-62 https://dx.doi.org/10.1007/s10495-014-1066-0 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_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.00 ASE AR 20 2014 1 26 11 50-62 |
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Enthalten in Apoptosis 20(2014), 1 vom: 26. Nov., Seite 50-62 volume:20 year:2014 number:1 day:26 month:11 pages:50-62 |
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Neuroblastoma mTOR inhibitor INK128 Chemotherapy Drug resistance |
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Zhang, Huiyuan @@aut@@ Dou, Jun @@aut@@ Yu, Yang @@aut@@ Zhao, Yanling @@aut@@ Fan, Yihui @@aut@@ Cheng, Jin @@aut@@ Xu, Xin @@aut@@ Liu, Wei @@aut@@ Guan, Shan @@aut@@ Chen, Zhenghu @@aut@@ shi, Yan @@aut@@ Patel, Roma @@aut@@ Vasudevan, Sanjeev A. @@aut@@ Zage, Peter E. @@aut@@ Zhang, Hong @@aut@@ Nuchtern, Jed G. @@aut@@ Kim, Eugene S. @@aut@@ Fu, Songbin @@aut@@ Yang, Jianhua @@aut@@ |
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The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. 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|
| author |
Zhang, Huiyuan |
| spellingShingle |
Zhang, Huiyuan ddc 570 bkl 44.00 misc Neuroblastoma misc mTOR inhibitor misc INK128 misc Chemotherapy misc Drug resistance mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling |
| authorStr |
Zhang, Huiyuan |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)306311577 |
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electronic Article |
| dewey-ones |
570 - Life sciences; biology |
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keep |
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aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
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springer |
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true |
| illustrated |
Not Illustrated |
| issn |
1573-675X |
| topic_title |
570 ASE 44.00 bkl mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling Neuroblastoma (dpeaa)DE-He213 mTOR inhibitor (dpeaa)DE-He213 INK128 (dpeaa)DE-He213 Chemotherapy (dpeaa)DE-He213 Drug resistance (dpeaa)DE-He213 |
| topic |
ddc 570 bkl 44.00 misc Neuroblastoma misc mTOR inhibitor misc INK128 misc Chemotherapy misc Drug resistance |
| topic_unstemmed |
ddc 570 bkl 44.00 misc Neuroblastoma misc mTOR inhibitor misc INK128 misc Chemotherapy misc Drug resistance |
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ddc 570 bkl 44.00 misc Neuroblastoma misc mTOR inhibitor misc INK128 misc Chemotherapy misc Drug resistance |
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Elektronische Aufsätze Aufsätze Elektronische Ressource |
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mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling |
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mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling |
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Zhang, Huiyuan Dou, Jun Yu, Yang Zhao, Yanling Fan, Yihui Cheng, Jin Xu, Xin Liu, Wei Guan, Shan Chen, Zhenghu shi, Yan Patel, Roma Vasudevan, Sanjeev A. Zage, Peter E. Zhang, Hong Nuchtern, Jed G. Kim, Eugene S. Fu, Songbin Yang, Jianhua |
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mtor atp-competitive inhibitor ink128 inhibits neuroblastoma growth via blocking mtorc signaling |
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mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling |
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Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. |
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Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. |
| abstract_unstemmed |
Abstract High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. |
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| score |
7.3989544 |