Role Of HGF/c-Met Signaling Pathway In Crizotinib-Induced Of Different Lung Adenocarcinoma Cell Lines

AIM:To investigate the role of HGF/c-Met signaling pathway in crizotinib-induced of different lung adenocarcinoma cell lines and analyze its potential regulation mechanisms.METHODS:Cell proliferation and cytotoxicity were measured by MTT assay; Apoptosis was assessed by flow cytometry with annexin V-PE/7AAD double staining at indicated doses of crizotinib was measured at different times points (24h,48h,72h); The expressions and activity levels of apoptosis-associated proteins of p-MET, p-AKT, p-ERK were determined at 24h, 48h,72h by Western blot analysis.RESULTS:1 MTT results showed: with the increase of concentration and action time of crizotinib, the inhibition rate of three cells are increased, the inhibition effect depended on dose and time. We calculated IC50 of H19993 and H2228, but we have not get IC50 of A549 in doses 10 times of crizotinib;2 Flow cytometry results showed: After 72 hours, the rate of apoptosis of H19993 and H2228 cells group, crizotinib treatment group were significantly higher than the control group and A549 cell group, it was statistically significant (p<0.05);3 Westblot results showed: After 72 hours, the expression levels of p-MET, p-AKT, p-ERK protein expression in H19993 and H2228 cells group with crizotinib were lower than control group, (p<0.05). The effects in A549 cell group were not significant, (p>0.05).CONCLUSION:Compared with A549 group, Crizotinib displayed a positive anti-tumor activity in H1993 and H2228 cell groups, it was speculated that the HGF/c-met pathway may play an important role of anti-tumor, crizotinib induces apoptosis though HGF/c-Met pathway in lung cancer cells, and it may contribute to MET target therapy.