Abstract: This study investigated the effect of tannic acid and cisplatin on PERK-ATF4 pathway of endoplasmic reticulum stress in hepatocellular carcinoma HepG2 cells and the molecular mechanism of tannic acid (TA) combined with cisplatin (CDDP) against hepatocellular carcinoma.HepG2 cells were cultured with 180 μM TA or/and 0.9 μg/mL CDDP for 24 h or 48 h.The levels of PERK,p-PERK,ATF4,CHOP,Procaspase3 and Cleaved caspase3 were analyzed by real-time fluorescence quantitative PCR (q-RT-PCR) and Western Blot.Q-RT-PCR and Western Blot results showed that the combination of TA and CDDP could significantly upregulate the expression levels of PERK,ATF4 and CHOP,the shear activation level of Caspase3,and downregulate the phosphorylation level of PERK (P<0.01 or P<0.05).The results indicated that TA can combine with CDDP to enhance the activation level of endoplasmic reticulum stress in hepatocellular carcinoma HepG2 cells by PERK-ATF4 pathway,which may be through the activation of ERS,promoting the expression of molecules related to PERK-ATF4 pathway and CHOP of ERS marker,inhibiting the phosphorylation of PERK,and promoting the shear activation of Caspase3 to induce apoptosis.

Key words: tannic acid, cis-dichlorodiamine platinum, hepatocellular carcinoma, endoplasmic reticulum stress, PERK-ATF4 pathway, Caspase3