Role of HGF/c-Met signaling pathway in crizotinib-induced apoptosis of different lung carcinoma cell lines
10.3969/j.issn.1000-4718.2016.03.010
- VernacularTitle:HGF／c-Met信号通路在克唑替尼诱导不同肺癌细胞株凋亡中的作用
- Author:
Zhixin DONG
;
Yani LI
;
Ruiling NING
;
Xiangqun SONG
;
Shaozhang ZHOU
- Publication Type:Journal Article
- Keywords:
HGF/c-Met signaling pathway;
H1993 cells;
H2228 cells;
Crizotinib;
Apoptosis
- From:
Chinese Journal of Pathophysiology
2016;32(3):445-450
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the role of HGF/c-Met signaling pathway in crizotinib-induced apoptosis of different lung carcinoma cell lines and to analyze its potential regulatory mechanisms .METHODS: EML4-ALK positive cell line H2228, c-Met proliferation cell line H1993 and control cell line A549 were treated with crizotinib at different doses for different time periods .The viability of the cell lines was measured by MTT assay .The apoptosis was analyzed by flow cytometry with PI staining.The protein levels of MET and phosphorylated MET (p-MET) of HGF/c-Met signaling pathway as well as its down-stream key proteins AKT , ERK, p-AKT and p-ERK in the cell lines before and after crizotinib treatment were examined by Western blot .RESULTS:The growth of H1993, H2228 and A549 cell lines was inhibited after crizoti-nib treatment for 72 h in a dose-dependent manner .Apoptotic rates of H1993 cells and H2228 cells were increased with the crizotinib concentration and exposure time .Down-regulation of p-MET, p-AKT and p-ERK at protein levels in H1993 cells and H2228 cells after exposure to crizotinib for 72 h was confirmed by Western blot .No obvious change of the related-pro-teins of HGF/c-Met signaling pathway was found in A 549 cell line.CONCLUSION: HGF/c-Met signaling pathway may contribute to crizotinib-induced apoptosis of H1993 cells and H2228 cells, which provides the experimental basis for MET-targeting treatment of lung cancer .
