Effects of metformin combined with celecoxib on the proliferation and apoptosis of hepatoma HepG2 and Huh7 cell lines / 中华肝胆外科杂志

ABSTRACT

Objective:To explore the effects and the mechanism of metformin combined with celecoxib on the proliferation and apoptosis of hepatoma HepG2 and Huh7 cells.Methods:Hepatoma cells HepG2 and Huh7 were divided into control group, metformin group, celecoxib group and combination medication group, CCK-8 assay was used to detect cell proliferation; Hoechst33258 staining method was used to investigate the cell apoptosis; wound healing test was used to detect cells migration ability; Transwell invasion chamber test was used to detect cell invasion ability; Western blotting was used to detect the expression of AMPK, PI3K, Akt, mTOR.Results:After metformin and celecoxib treatment, HepG2 and Huh7 cells were gradually contracted, disintegrated and more apoptotic cells were noticed, and cell proliferation was significantly inhibited. The wound healing test results showed that the cell migration was significantly decreased ( P<0.05) under metformin and celecoxib treatment. The results of the transwell invasion chamber test showed that the metformin and celecoxib treatment inhibited the invasion of HepG2 and Huh7 cells ( P<0.05). The expression levels of AKT, AMPK, and mTOR were decreased in HepG2 cells in the combinational treatment group, and the expression level of PI3K was decreased and then increased; the expression levels of AKT, AMPK, PI3K, and mTOR in Huh7 cells were decreased. Conclusions:Metformin can cooperate with celecoxib to enhance the inhibitory effect on the proliferation, migration and invasion of HepG2 and Huh7 cells. The mechanism may be related to the inhibition of the expression of mTOR signaling pathway.