Suberoylanilide hydroxamic acid induces apoptosis of HepG2 cells by en-doplasmic reticulum stress apoptotic pathway / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of suberoylanilide hydroxamic acid ( SAHA) on the proliferation and apoptosis of human hepatocellular carcinoma HepG 2 cells and to explore its possible mechanism .METHODS: HepG2 cells were treated with SAHA at different concentrations for 48 h.The proliferation of HepG2 cells was detected by real-time cellular analysis.The protein levels of acetylated histones H3K9 and H3K27, glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase ( PERK ) and p-PERK were determined by Western blot .The cell apoptosis was analyzed by flow cytometry .RESULTS:Compared with control group , treatment with SAHA at 0.1μmol/L and 1 μmol/L for 48 h showed no significant inhibitory effect on the proliferation of HepG 2 cells, while SAHA at 6 μmol/L and 12 μmol/L significantly inhibited the proliferation of HepG 2 cells (P<0.05).The results of Western blot showed that the protein levels of acH3K9, acH3K27, GRP78 and p-PERK increased significantly after treated with SAHA at diffe-rent concentrations for 48 h, while the protein level of PERK was decreased significantly (P<0.05).The results of flow cytometry analysis showed that the apoptotic rates of the HepG 2 cells increased with the increase in SAHA concentration . CONCLUSION:SAHA up-regulates the acetylation of H3K9 and H3K27 in the HepG2 cells and induces apoptosis of HepG2 cells by activating the endoplasmic reticulum stress-related apoptosis pathway .