【摘要】 目的研究缺氧诱导因子-1α(hypoxia inducible factor1α,HIF-1α)反义寡核苷酸(antisense ol-igodexynucleotide,ASODN)对人胃癌细胞凋亡及化疗药物敏感性的影响。方法人工合成HIF-1αASODN经阳离子脂质体包裹后瞬时转染人胃癌SGC-7901细胞系。采用RT-PCR和免疫细胞化学检测转染后HIF-1α基因表达情况,MTT法观察化疗药物敏感性的变化,AO/EB染色及TUNEL检测SGC-7901细胞转染后顺铂诱导的凋亡。结果经HIF-1αASODN处理的SGC-7901细胞HIF-1α基因表达明显下调,HIF-1αASODN处理的SGC-7901细胞加顺铂作用后与对照组比较,细胞凋亡率明显增加,化疗药物敏感性增强。结论阳离子脂质体转染HIF-1αASODN具有促进化疗药物诱导胃癌SGC-7901细胞凋亡及增强化疗药物敏感性作用。更多还原

【Abstract】 Objective To investigate the effects of antisense oligodeoxynucleotide targeting HIF-1α on apoptosis and chemotherapy sensitivity of gastric carcinoma SGC-7901.Methods Antisense ODN and sense ODN were constructed and transfected into SGC-7901 cells by Dosper liposomal reagent.The changes of HIF-1α gene expression were observed by RT-PCR and immunocytochemistry.The cytotoxicity of Cisplatin was determined by MTT,while apoptosis indexes were detected by using terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL).Results Protein and mRNA of HIF-1α in SGC-7901 were downregulated by HIF-1α ASODN.The proliferation inhibition rate of Cisplatin in combination with HIF-1α ASODN was ( 72.5 ± 4.8 )%,but ( 30.7 ± 2.9 )%,( 34.2 ± 3.5 )% or ( 38.6 ± 3.1 )% in untreated control group,liposomes group and sense ODN group respectively.TUNEL showed that the apoptosis index in ASODN group was ( 42.0 ± 3.5 )%.HIF-1α ASODN achieved the strongest effects to enhance apoptosis when compared with control groups(P< 0.01 ).Conclusion HIF-1αASODN could inhibit the proliferation,induce the apoptosis and enhance the sensitivity of gastric carcinoma cell line SGC-7901 to cisplatin.Antisense therapy targeting HIF-1α in combination with chemotherapy maybe a very promising strategy for gastric carcinoma therapy.更多还原