关键词: 胃癌, 增殖, 凋亡, 缺氧诱导因子-1α, 细胞程序性死亡受体-配体1

Abstract: Objective To investigate the effect of small molecule interfering RNA(siRNA)on the proliferation,apoptosis,and programmed cell death-ligand 1(PD-L1)expression of gastric cancer(GC)MGC-803 cells by targeting hypoxia inducible factor-1α(HIF-1α). Methods Cancer and adjacent normal tissues were collected from 35 GC patients.The mRNA expression of patients HIF-1α and PD-L1 was detected,and their correlation was further analyzed.HIF-1α mRNA expression was examined in different GC cell lines,and MGC-803 cells were selected for subsequent experiments.MGC-803 cells were divided into the following groups:normal group,hypoxia group,hypoxia+si-NC group,hypoxia+si-HIF-1α group,hypoxia+si-HIF-1α+pcDNA group,and hypoxia+si-HIF-1α+pcDNA-PD-L1 group.Cell proliferation,apoptosis and related protein expression were assessed.A nude mouse xenograft model was established to verify in vivo effects. Results Compared with those in the adjacent normal tissues,the HIF-1α and PD-L1 mRNA expression levels in the GC tissues were increased,and they were positively correlated(P<0.05).The expression levels of HIF-1α mRNA and protein were higher in MKN-45,SGC-7901,AGS,HGC-27,and MGC-803 cells than in GES-1 cells(P<0.05),with MGC-803 exhibiting the highest expression levels.Silencing HIF-1α downregulated PD-L1 expression in MGC-803 cells under hypoxic conditions,reduced proliferation activity and the expression of proliferating cell nuclear antigen and Bcl-2,and increased apoptosis rate and the expression of Bax and Cleaved-Caspase-3(P<0.05).Silencing HIF-1α reduced xenograft tumor volume,weight,and PD-L1 positive expression rate in nude mice(P<0.05).Overexpression of PD-L1 reversed the above effects. Conclusion Knockdown of HIF-1α expression under hypoxic conditions can downregulate PD-L1 expression,inhibit GC cell proliferation,and promote cell apoptosis.

Key words: gastric cancer, proliferation, apoptosis, hypoxia inducible factor-1α, programmed cell death-ligand 1