Effects Of Metformin On Proliferation Of Human Hepatocma Cell Line HepG2and Expression Of REDD1and CyclinD1

Objective：To investigate the effects of metformin on proliferation of humanhepatoma cell line HepG2and the expression of REDD1and cyclinD1.Methods： HepG2cells were cultured in vitro and treated with differectconcentrations of metformin (0.0，2.5，5.0，10.0mmol/L). Changes in cellproliferation and cell cycle distribution were evaluated by MTT assay and flowcytometry, respectively.The expression levels of mRNA of REDD1and cyclinD1were detected by Reverse Transcription-Polymerase Chain Reaction （RT-PCR）and the expression levels of proteins of REDD1and cyclinD1were detected byWestern blot.Results：HepG2cells were treated with metformin for48hour， and theproliferation of HepG2cells was markedly inhibited in the metformin-treated groups(P＜0.05)， and the number of HepG2cells in the G1phase was significantlyhigher， compared with the control group(P＜0.05). Meanwhile， the mRNAexpressions of REDD1in three metformin-treated groups were significantly up-regulated， compared with those in control group(P＜0.01)， and the mRNAexpressions of cyclinD1were significantly down-regulated(P＜0.05)；the proteinexpressions of REDD1were significantly up-regulated in the metformin-treatedgroups(P＜0.01)，and the protein expressions of cyclinD1were significantly down-regulated(P＜0.01).Conclusion：Metformin inhibited the proliferation of HepG2cells and inducedcell cycle arrest at G1phase， and metformin significantly up-regulated theexpressions of REDD1and down-regulated the expressions of cyclinD1，in a doesdependent manner.