BIM induction of apoptosis triggered by EGFR-sensitive and resistance cell lines of non-small-cell lung cancer |
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Authors: | Li Zhanxia Zhou Songwen Zhang Ling Su Chunxia Hang Jinqin Zhao Yinmin Su Bo Zhou Caicun |
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Institution: | (1) Department of Oncology; Pulmonary Hospital, Tongji University School of Medicine, 507# Zhengmin Road, Yangpu Region, Shanghai, 200433, China;(2) Department of Respiration, Putuo District, People’ Hospital, Shanghai, 200060, China;(3) Research Institute of Lung Cancer, Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China; |
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Abstract: | We sought to improve the understanding of oncogene-dependent and independent non-small-cell lung cancer (NSCLC), which could
provide insight into mechanism of sensitivity and/or resistance to tyrosine kinase inhibitors or chemotherapeutics. NSCLC
cell lines with different EGFR genotypes were used in this study; MTT assay and flow cytometry were applied to study the sensitivities
of these cell lines to gefitinib and cisplatin. Western blot was performed to determine the expression levels of BIM and other
Bcl-2 family proteins pre- and pro-treatment. Gefitinib provoked apoptosis of caspase activation via the intrinsic pathways
and significantly up-regulated expression of BIM protein in drug-sensitive PC-9 cell line, but not resistant PC-9/BB4 cell
line. The knockdown of BIM expression by RNA interference virtually eliminated gefitinib-induced cell killing in PC-9 cells
in vitro. Cisplatin could induce apoptosis of the cell lines, including H1299, A549, PC-9, and PC-9/BB4 cells, but which was
not associated with overexpression of BIM. BIM is involved in TKI-induced apoptosis in sensitive EGFR-mutant cell line. Down-regulation
of BIM and resistance to gefitinib were both seen in the acquired resistant PC-9/BB4 cell line. The induction of BIM may have
a role in the treatment of TKI-resistant tumors. |
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