The efficacy of blocking PD-L1 in the treatment of primary hepatocellular carcinoma with oxaliplatin
YIN Changjie
GAO Hui
LI Hua
YUAN Weiwei
JIANG Chaoyang
ZHOU Jinjun
CHEN Yulin
WANG Tao
WANG Dan
ZHANG Tao
Abstract：This study was designed to investigate the efficacy of blocking PD-L1 in the treatment of primary hepatocellular carcinoma(HCC) with oxaliplatin (L-OHP) and its mechanisms.HepG2 cells were treated with L-OHP,and then qRT-PCR and Western blotting were employed to detect the expression of PD-L1 and the level of p-ERK1/2.The mouse xenografts model of HCC was established by Hepa1-6 cells,and divided into 4 groups randomly:control group,L-OHP group,anti-PD-L1 group,L-OHP+anti-PD-L1 group.Average tumor volume and tumor inhibitory rate were calculated after treatment in all groups.qRT-PCR and Western blot were employed to measure the expression of PD-L1 after promoting or inhibiting the phosphorylation of ERK1/2 of HepG2 and Hepa1-6.Data showed that L-OHP could inhibit the growth of HepG2 cells observably,with IC50 value of 20.94 mg/L.The treatment of L-OHP could increase p-ERK1/2 and PD-L1 (P＜0.05).In mouse xenografts models of HCC,L-OHP+anti-PD-L1 group demonstrated less average tumor volume (P＜0.05),higher tumor inhibitory rate (P＜0.05)and longer survival time (P＜0.05),as compared with control group.After promoting or inhibiting the phosphorylation of ERK1/2 of HepG2,the expression of PD-L1 was obviously elevated or reduced,correspondingly.In conclusion,L-OHP could up-regulate the expression of PD-L1 in HCC cells via increasing the level of ERK1/2 phosphorylation and result in treatment failure,while combination with anti-PD-L1 could enhance the effect of anti-HCC of L-OHP.
Keywords：PD-L1OxaliplatinPrimary hepatocellular carcinomaERK1/2 phosphorylation
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1066-1070 )