医学分子生物学杂志2026，Vol.23Issue(4)：398-405,8.DOI:10.3870/j.issn.1672-8009.2026.04.004
siRNA靶向干扰HIF-1α对胃癌细胞增殖、凋亡及PD-L1表达的影响
Effects of siRNA-Mediated HIF-1α Inhibition on Gastric Cancer Cell Proliferation,Apoptosis,and PD-L1 Expression
摘要
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 pa-tients 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 lev-els.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 prolif-eration,and promote cell apoptosis.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1Key words
gastric cancer/proliferation/apoptosis/hypoxia inducible factor-1α/pro-grammed cell death-ligand 1分类
医药卫生引用本文复制引用
刘院刚,王首星,李欣,温进平,杨朝鑫..siRNA靶向干扰HIF-1α对胃癌细胞增殖、凋亡及PD-L1表达的影响[J].医学分子生物学杂志,2026,23(4):398-405,8.基金项目
河北省卫生健康委医学科学研究(No.20220481) This work was supported by a grant from the Medical Scientific Research Project of Hebei Provincial Health Commission(No.20220481). （No.20220481）
