Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway.

Abstract

The ability of metformin, an antidiabetic drug with wide applications, to inhibit tumor cell growth has recently been discovered. The PI3K/Akt signaling pathway has been found to play an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore the effect of metformin on the proliferation of A431 human squamous cell carcinoma cells and the underlying molecular mechanisms. A431 cells in the logarithmic growth phase were treated with 0, 15, 30, 45 and 60 mM metformin for 12, 24 and 36 h, respectively. Cell morphology with 45 mM metformin treatment for 24 h was observed under a microscope. The proliferation of A431 cells was detected by the Cell Counting kit-8 colorimetric method. The mRNA expression levels of PI3K and Akt were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of PI3K, Akt and phosphorylated (p)-Akt were detected by western blot analysis. Metformin treatment caused morphological change in A431 cells and inhibited their proliferation in a significant time- and dose-dependent manner. RT-PCR results showed that the mRNA expression of PI3K was inhibited by metformin in a time- and dose-dependent manner (P<0.05). However, there was no significant change in the mRNA expression of Akt following metformin treatment (P>0.05). Western blotting results showed that the protein expression levels of PI3K and p-Akt were inhibited by metformin in a time- and dose-dependent manner (P<0.05). In conclusion, metformin significantly inhibited the proliferation of A431 cells in the current study, which may be strongly associated with the inhibition of the PI3K/Akt signaling pathway.