【摘要】 目的探讨反义HIF-1α基因对人肝癌裸鼠皮下移植瘤的影响及其相关机制。方法使用人原发性肝癌细胞株SMMC-7 7 2 1建立人肝癌裸鼠皮下移植瘤动物模型。待肿瘤生长至直径约0.4cm时,将荷瘤裸鼠随机分为3组,分别注射生理盐水、质粒PcDNA 3和HIF-1α/PcDNA 3 B,质粒用脂质体DOTAP介导转染细胞。观察各组动物的肿瘤生长曲线;取肿瘤标本作免疫组织化学检查(SABC法)及蛋白质印迹检查,检测各组肿瘤的VEGF和HIF-1α表达及微血管密度(MVD)和细胞凋亡。结果HIF-1α/PcDNA 3 B治疗组各时点的肿瘤体积,以及肿瘤组织中HIF-1α蛋白、MVD,VEGF表达均低于对照组,而细胞凋亡指数高于对照组,差异均有显著性(P<0.0 5)。结论通过阻断癌细胞的缺氧适应途径,反义HIF-1α基因治疗肝癌有抑制肿瘤生长、抑制肿瘤血管生成及诱导细胞凋亡的作用。更多还原

【Abstract】 Objective To observe the effects and mechanism of antisense HIF-1α gene on implanted human primary hepatic carcinoma of nude mouse.Methods Tumors were established by subcutaneous injection of 3×10~6 tumor cells,named SMMC-7721,into the back of nude mice.Once the tumor grew to 0.4cm in(diameter),the mice were divided randomly into three groups with injected respectively with NS、empty plamid PcDNA3、and antisense HIF-1α plasmid.Half group of the nude mice were used to observe the tumor growth curve,and the other half were to obtain the tumor samples to be used in the examinations of the expression of angiostatin、HIF-1α,VEGF,MVD and cell apoptosis.Results Tumors grew rapidly in the control group than that in the antisense HIF-1α group.In antisense HIF-1α gene therapy resulted in low expression of HIF-1α,MVD and VEGF than those in 2 control groups(P<0.05~0.01);but in HIF-1α group.AI was higher than that in the control group(P<0.01).Conclusions Antisense HIF-1α gene therapy is a promising approach to treat human liver cancer by suppression of tumor growth and tumor angiogenesis and by induction of cell apoptosis.更多还原