Abstract: Objective The Objective of this study was to explore the role of tetrandrine in lung cancer and its molecular mechanism.Methods The MTS method was used to detect the proliferation of lung cancer H1299 cells and A549 cells treated with tetrandrine at 10,15,20,30,40 and 60 μM/L,and then the activities of Caspase3,Caspase8 and Caspase9 were detected by kits,and apoptosis was examined by TUNEL kit.In order to study the mechanism of tetrandrine,Western blot was used to detect the expression of MAPK signaling pathways(p-Akt,PI3K,mTOR and Akt proteins),proliferation and metastasis(MMP-2,MMP-9,PCNA,Cyclin D1 and P21 proteins),cell cycle and apoptosis related proteins(Cyclin D2,Bcl-2,MCL-1,Bax and p53 proteins).Finally,Real-time PCR was used to detect the mRNA expression of PI3k,mTOR,MMP-2,MMP-9,PCNA,Cyclin D1,Cyclin D2,MCL-1,Bax,Bcl-2 and TP53.Results Tetrandrine could inhibit the proliferation of lung cancer H1299 and A549 cells,induce apoptosis,and increase the activities of Caspase3,Caspase8 and Caspase9 in H1299 cells and A549 cells.After treatment with tetrandrine,the expression of PI3K,p-Akt,mTOR,MMP-2,MMP-9,PCNA,Cyclin D1,Cyclin D2and Bcl-2 proteins were reduced,and the expression of P21,MCL-1,Bax and p53 proteins were increased,showing a dose-dependent manner,but no effect on the expression of Akt protein.The mRNA expression of PI3K,mTOR,MMP-2,MMP-9,PCNA,Cyclin D1,Cyclin D2 and Bcl-2 was decreased,and the mRNA expression of TP53,MCL-1 and Bax was increased in H1299 cells and A549 cells.Conclusion Tetrandrine inhibits cell proliferation and induces apoptosis by regulating the MAPK signaling pathway,proliferation and metastasis,cell cycle and apoptosis related proteins and genes expression.

Key words: Tetrandrine, Lung cancer, Molecular mechanism