Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC
Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection o...
Ausführliche Beschreibung
Autor*in: |
LIU Jiaxin [verfasserIn] LI Shanshan, [verfasserIn] WANG Dong [verfasserIn] |
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Chinesisch |
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2022 |
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In: 陆军军医大学学报 - Editorial Office of Journal of Army Medical University, 2022, 44(2022), 24, Seite 2500-2506 |
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Übergeordnetes Werk: |
volume:44 ; year:2022 ; number:24 ; pages:2500-2506 |
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DOI / URN: |
10.16016/j.2097-0927.202209006 |
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DOAJ004494237 |
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520 | |a Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. | ||
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10.16016/j.2097-0927.202209006 doi (DE-627)DOAJ004494237 (DE-599)DOAJ43e7f0c7dd4b4ddc88e6ea2c745e6824 DE-627 ger DE-627 rakwb chi R5-920 LIU Jiaxin verfasserin aut Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. alk targeted therapy crizotinib resistance murine double minute 2 epithelial mesenchymal transition Medicine (General) LI Shanshan, verfasserin aut WANG Dong verfasserin aut In 陆军军医大学学报 Editorial Office of Journal of Army Medical University, 2022 44(2022), 24, Seite 2500-2506 (DE-627)DOAJ078594804 20970927 nnns volume:44 year:2022 number:24 pages:2500-2506 https://doi.org/10.16016/j.2097-0927.202209006 kostenfrei https://doaj.org/article/43e7f0c7dd4b4ddc88e6ea2c745e6824 kostenfrei http://aammt.tmmu.edu.cn/Upload/rhtml/202209006.htm kostenfrei https://doaj.org/toc/2097-0927 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 44 2022 24 2500-2506 |
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10.16016/j.2097-0927.202209006 doi (DE-627)DOAJ004494237 (DE-599)DOAJ43e7f0c7dd4b4ddc88e6ea2c745e6824 DE-627 ger DE-627 rakwb chi R5-920 LIU Jiaxin verfasserin aut Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. alk targeted therapy crizotinib resistance murine double minute 2 epithelial mesenchymal transition Medicine (General) LI Shanshan, verfasserin aut WANG Dong verfasserin aut In 陆军军医大学学报 Editorial Office of Journal of Army Medical University, 2022 44(2022), 24, Seite 2500-2506 (DE-627)DOAJ078594804 20970927 nnns volume:44 year:2022 number:24 pages:2500-2506 https://doi.org/10.16016/j.2097-0927.202209006 kostenfrei https://doaj.org/article/43e7f0c7dd4b4ddc88e6ea2c745e6824 kostenfrei http://aammt.tmmu.edu.cn/Upload/rhtml/202209006.htm kostenfrei https://doaj.org/toc/2097-0927 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 44 2022 24 2500-2506 |
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10.16016/j.2097-0927.202209006 doi (DE-627)DOAJ004494237 (DE-599)DOAJ43e7f0c7dd4b4ddc88e6ea2c745e6824 DE-627 ger DE-627 rakwb chi R5-920 LIU Jiaxin verfasserin aut Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. alk targeted therapy crizotinib resistance murine double minute 2 epithelial mesenchymal transition Medicine (General) LI Shanshan, verfasserin aut WANG Dong verfasserin aut In 陆军军医大学学报 Editorial Office of Journal of Army Medical University, 2022 44(2022), 24, Seite 2500-2506 (DE-627)DOAJ078594804 20970927 nnns volume:44 year:2022 number:24 pages:2500-2506 https://doi.org/10.16016/j.2097-0927.202209006 kostenfrei https://doaj.org/article/43e7f0c7dd4b4ddc88e6ea2c745e6824 kostenfrei http://aammt.tmmu.edu.cn/Upload/rhtml/202209006.htm kostenfrei https://doaj.org/toc/2097-0927 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 44 2022 24 2500-2506 |
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10.16016/j.2097-0927.202209006 doi (DE-627)DOAJ004494237 (DE-599)DOAJ43e7f0c7dd4b4ddc88e6ea2c745e6824 DE-627 ger DE-627 rakwb chi R5-920 LIU Jiaxin verfasserin aut Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. alk targeted therapy crizotinib resistance murine double minute 2 epithelial mesenchymal transition Medicine (General) LI Shanshan, verfasserin aut WANG Dong verfasserin aut In 陆军军医大学学报 Editorial Office of Journal of Army Medical University, 2022 44(2022), 24, Seite 2500-2506 (DE-627)DOAJ078594804 20970927 nnns volume:44 year:2022 number:24 pages:2500-2506 https://doi.org/10.16016/j.2097-0927.202209006 kostenfrei https://doaj.org/article/43e7f0c7dd4b4ddc88e6ea2c745e6824 kostenfrei http://aammt.tmmu.edu.cn/Upload/rhtml/202209006.htm kostenfrei https://doaj.org/toc/2097-0927 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 44 2022 24 2500-2506 |
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10.16016/j.2097-0927.202209006 doi (DE-627)DOAJ004494237 (DE-599)DOAJ43e7f0c7dd4b4ddc88e6ea2c745e6824 DE-627 ger DE-627 rakwb chi R5-920 LIU Jiaxin verfasserin aut Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. alk targeted therapy crizotinib resistance murine double minute 2 epithelial mesenchymal transition Medicine (General) LI Shanshan, verfasserin aut WANG Dong verfasserin aut In 陆军军医大学学报 Editorial Office of Journal of Army Medical University, 2022 44(2022), 24, Seite 2500-2506 (DE-627)DOAJ078594804 20970927 nnns volume:44 year:2022 number:24 pages:2500-2506 https://doi.org/10.16016/j.2097-0927.202209006 kostenfrei https://doaj.org/article/43e7f0c7dd4b4ddc88e6ea2c745e6824 kostenfrei http://aammt.tmmu.edu.cn/Upload/rhtml/202209006.htm kostenfrei https://doaj.org/toc/2097-0927 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ AR 44 2022 24 2500-2506 |
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overexpression of mdm2 induces crizotinib resistance in targeted therapy for alk-positive nsclc |
callnumber |
R5-920 |
title_auth |
Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC |
abstract |
Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. |
abstractGer |
Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. |
abstract_unstemmed |
Objective To investigate the effect of overexpression of murine double minute 2 (Mdm2) on the sensitivity to crizotinib in the anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) cell line H3122. Methods H3122 cells with Mdm2 overexpression were established by transfection of plasmid encoding Mdm2, and the H3122 cells transfected with empty vector (EV) served as control cells. After the Mdm2 overexpression cells and control cells were treated with different concentrations of crizotinib, an ALK inhibitor, MTT assay, colony formation assay and TUNEL assay were applied to evaluate the sensitivity to crizotinib. Western blotting was used to detect the expression of ALK, its downstream proteins and biomarkers in epithelial mesenchymal transition (EMT). Results Compared with the control cells, the H3122 cells with Mdm2 overexpression were resistant to crizotinib treatment, and were tolerant to crizotinib-induced apoptosis. Biochemical analysis of signaling transduction suggested that overexpression of Mdm2 failed to restore the phosphorylation of ALK and downstream molecules. Overexpression of Mdm2 also resulted in EMT and acquisition of mesenchymal phenotype in H3122 cells. Conclusion Overexpression of Mdm2 leads to resistance to crizotinib in H3122 cells probably through the induction of EMT process. |
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title_short |
Overexpression of Mdm2 induces crizotinib resistance in targeted therapy for ALK-positive NSCLC |
url |
https://doi.org/10.16016/j.2097-0927.202209006 https://doaj.org/article/43e7f0c7dd4b4ddc88e6ea2c745e6824 http://aammt.tmmu.edu.cn/Upload/rhtml/202209006.htm https://doaj.org/toc/2097-0927 |
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LI Shanshan WANG Dong |
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LI Shanshan WANG Dong |
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R - General Medicine |
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10.16016/j.2097-0927.202209006 |
callnumber-a |
R5-920 |
up_date |
2024-07-03T23:57:51.010Z |
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