Anti-tumor effect of icotinib combined with metformin on non-small cell lung cancer H1975 cells
AIM To study the anti-tumor effect of icotinib combined with metformin on non-small cell lung cancer(NSCLC)H1975 cells and its possible mechanism.METHODS CCK-8 assay was used to detect the proliferation inhibitory effect and combination index(CI)of icotinib monotherapy(0,0.1,1,5,10,20,40 μmol·mL-1),metformin monotherapy(0,2,4,8,16,32,64 mmol·mL-1),and icotinib(0,0.125,0.25,0.5,1 times of IC50)combined with metformin(0.5 times of IC50)on the H1975 cells.The migratory ability of the cells was detected by scratch test,and the invasive ability of the cells was detected by invasion test.Annexin V-FITC/PI flow cytometry was used to detect the rate of apoptosis.Western blot was used to detect the expression level of related proteins.RESULTS The IC5o of icotinib and metformin for the inhibition on H1975 cells after 48 h were(49.90±4.84)μmol·mL-1 and(13.20±1.27)mmol·mL-1,respectively.Icotinib and metformin produced a synergistic effect in H1975 cells(CI＜1).Compared with the metformin group and the icotinib group,the migration rate and invasion ability of combination group were significantly decreased,and the apoptosis rate was significantly increased(P＜0.05);the expression of p-Akt,p-mTOR and Bcl-2 were significantly decreased,while the expression of p-AMPK and Bax were significantly increased(P＜0.05).CONCLUSION Icotinib and metformin have significant synergic antitumor effects and proapoptotic effects on non-small cell lung cancer H1975 cells,and the underlying mechanism may be related to enhancing activation of AMPK and inhibition of Akt/mTOR signaling pathway.
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