Effect of afatinib on the proliferation and apoptosis of human breast cell lines and its mechanisms
10.3969/j.issn.1000-8179.2017.15.422
- VernacularTitle:阿法替尼对人乳腺癌细胞增殖与凋亡的影响及机制研究
- Author:
Ying ZHAO
;
Jiangrui CHI
;
Hongmeng ZHAO
;
Bin ZHANG
;
Yue YU
;
Xuchen CAO
- Keywords:
breast neoplasm;
afatinib;
cell cycle;
apoptosis
- From:
Chinese Journal of Clinical Oncology
2017;44(15):739-743
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of afatinib, a tyrosine kinase inhibitor, on the proliferation, cell cycle, and apoptosis of human breast cell lines, and compare its effects with those of gefitinib. Methods:Three human breast cell lines, MCF-7, T47D, and MDA-MB-231, were cultured as cell models. A methyl thiazolyl tetrazolium assay was utilized to measure cell viability. Flow cytometer was used to analyze the cell cycle arrest (PI staining) and apoptosis rates (Annexin-V/PI staining). The protein expression was detected by Western blot analysis. Results:The proliferation of three human breast cell lines was significantly inhibited by afatinib, and the IC50 levels of MCF-7, T47D, and MDA-MB-231 were 0.101, 0.141, and 0.887μmol/L, respectively. The G0/G1 phase cell ratio increased con-siderably 24 h after afatinib was added to T47D or MDA-MB-231. The cell apoptosis rate also increased in the two cell lines (88.9%and 58.1%). The cleavage of apoptosis pathway proteins PARP and caspase-3 was also promoted by afatinib. Phosphorylation of EGFR was significantly inhibited by afatinib in the MDA-MB-231 cell line. Finally, the inhibition effect of afatinib was stronger than that of gefi-tinib. Conclusion: Afatinib could significantly inhibit the proliferation of breast cancer cells and promote apoptosis. The effect was dose-dependent. Afatinib was a more effective tyrosine kinase inhibitor as compared with gefitinib.
