缺氧诱导因子-1α反义寡核苷酸对胶质瘤细胞化疗敏感性的影响  

Antisense oligodexynucleotide targeting hypoxia inducible factor 1 α gene enhances the sensitivity of human glioma cells to cisplatin

作　　者：杨卫忠[1] 杨贤义[1] 石松生[1] 陈春美[1] 

机构地区：[1]福建医科大学附属协和医院神经外科,福州350001

出　　处：《中华实验外科杂志》2005年第9期1105-1106,共2页Chinese Journal of Experimental Surgery

摘　　要：目的研究缺氧诱导因子(HIF)1α反义寡核苷酸(ASODN)对人胶质瘤细胞化疗药物敏感性的影响。方法人工合成HIF1αASODN经阳离子脂质体包裹后瞬时转染人胶质瘤细胞株U251。采用RTPCR和免疫细胞化学检测转染后HIF1α基因表达,噻唑蓝(MTT)检测细胞增殖抑制率(PI),亚啶橙/溴化乙锭(AO/EB)染色及末端标记法(TUNEL)检测U251细胞转染后顺铂诱导的细胞凋亡指数(AI)。结果HIF1αASODN转染使U251细胞HIF1α基因表达明显下调,其AI和PI分别为(42.0±3.5)%和(72.5±4.8)%,,与各对照组比较均差异有统计学意义(P<0.01),而空白对照组,脂质体组和SODN组的AI和PI分别为(7.1±0.3)%,(8.2±0.2)%,(12.3±0.4)%和(30.7±2.9)%,(34.2±3.5)%,(38.6±3.1)%,AI和PI在各对照组之间的差异无统计学意义(P>0.05)。结论阳离子脂质体转染HIF1αASODN具有促进化疗药物诱导胶质瘤U251细胞凋亡及增强化疗药物敏感性作用。Objective To investigate the effect of antisense oligodeoxynucleotide targeting hypoxia inducible factor 1α on chemotherapy sensitivity of glioma cell line U251. Methods Antisense ODN and sense ODN were constructed and transfected into U251 cells by Dosper liposomal reagent. The HIF-lα gene expression was detected by RT-PCR and immunocyto-chemistry. The proliferative index （PI） was determined by MTT, while apoptosis indexes （AI） was detected by using terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. Results The protein and mRNA expression of HIF-lα in U251 cells was downregulated by HIF-1αASODN. The AI and PI in Cisplatin plus HIF-1αASODN group was （42.0±3.5） % and （72.5±4.8） % respectively, significantly higher than those in control groups （P〈0.01）.TheAI andPI were （7.1±0.3）%,（8.2±0.2）%,（12.3±0.4）% and （30.7±2.9） %, （34.2±3.5） %, （38.6±3.1） % in blank group, liposomes group and sense ODN group respectively. Conclusion HIF-1αASODN could inhibit the proliferation, induce the apoptosis and enhance the sensitivity of U251 to cisplatin. Antisense therapy targeting HIF-1α in combination with chemotherapy may be a very promising strategy for malignant glioma therapy.

关 键 词：胶质瘤 寡聚核苷酸 反义 缺氧诱导因子-1 脱噬作用 顺铂 人胶质瘤细胞 Α反义寡核苷酸 化疗敏感性 HIF-1α 

分 类 号：R73-3[医药卫生—肿瘤]