Effects of antidiabetic drug metformin on human lung adenocarcinoma cell A549 proliferation and apoptosis in vitro / 中国癌症杂志

ABSTRACT

Background and purpose:Metformin is known to be an insulin sensitization agent and is a fi rst line treatment for patients with type 2 diabetes. Recent clinical studies have revealed that metformin treatment has been associated with reduced cancer risk,which indicated that metformin may be a potential anti-neoplastic agent. We investigated the effects of antidiabetic drug metformin on proliferation and apoptosis in human lung adenocarcinoma cell line A549 in vitro and explored the possible underlying mechanisms. Methods:A549 cells were treated with 0.5 mmol/L,2 mmol/L and 8 mmol/L metformin for 48 hrs. Growth inhibition rates of the cells were measured by MTT assay. Cell apoptosis were detected by ? ow cytometery(FCM). Expressions of three genes including p53,Bcl-2 and Bax mRNA in the cells were measured by Real-Time PCR. Results:The proliferation of A549 cells was inhibited by metformin in a dose-dependent manner. The Inhibition rates of metformin at dosage of 0.5 mmol/L,2 mmol/L and 8 mmol/L group were (29?5)%,(68?3)% and (84.1?2.6)%,respectively. Apoptosis was induced when the cells were treated with moderate to high concentrations of metformin.The percentage of cells in early and late stage of apoptosis was increased from (1.1?0.3)% and (1.78?0.22)% in controlled group to (2.1?0.5)% and (9?4)% in metformin 8 mmol/ L group,respectively. The expressions of p53,Bcl-2 and Bax mRNA were all up-regulated after metformin treatment while the Bcl-2/Bax ratio was signifi cantly decreased. Conclusion:Metformin can inhibit the proliferation of human adenocarcinoma cancer cell line A549 and induce cell apoptosis with moderate to high drug concentrations in vitro,which may partly be attributed to the up-regulation of p53 and down-regulation of the Bcl-2/Bax ratio.