HIF-1α反义寡核苷酸治疗人胃癌裸鼠移植瘤的实验研究  

Experimental Study of HIF-1α Antisense Oligonucleotide on Implanted Human Gastric Cancer in Nude Mice

作　　者：何涛[1] 李永浩 王殿栋[3] 张虎[3] 

机构地区：[1]包头医学院第一附属医院普外科,包头014010 [2]平顶山煤业集团总医院普外科,平顶山467000 [3]包头医学院,包头014010

出　　处：《四川大学学报（医学版）》2010年第1期49-52,76,共5页Journal of Sichuan University(Medical Sciences)

基　　金：内蒙古自治区教育厅项目(NJZY07125)资助

摘　　要：目的研究缺氧诱导因子-1α(HIF-1α)反义寡核苷酸对人胃癌裸鼠皮下移植瘤的治疗作用。方法用人胃癌细胞株SCG-7901建立胃癌裸鼠皮下移植瘤模型,将荷瘤裸鼠随机分为反义寡核苷酸(ASOND)组、正义寡核苷酸(SOND)组和对照组,瘤体内分别注射阳离子脂质体包裹的HIF-1αASOND、HIF-1αSOND和空白阳离子脂质体。观察各组动物的肿瘤生长曲线,测瘤重计算抑瘤率,光学显微镜下观察肿瘤细胞形态学变化,免疫组化方法检测各组肿瘤组织HIF-1α、血管内皮生长因子(VEGF)和微血管密度(MVD)的表达。结果ASOND组裸鼠的肿瘤生长受到明显抑制,ASOND组瘤重与对照组比较差异有统计学意义(P<0.05);ASOND组、SOND组抑瘤率分别为47.94%、16.88%,差异有统计学意义(P<0.01);ASOND组肿瘤组织中HIF-1α、VEGF和MVD的表达低于SOND组和对照组(P<0.01)。结论肿瘤原位注射HIF-1α反义寡核苷酸治疗胃癌裸鼠皮下移植瘤能降低HIF-1α的表达,继而减少VEGF的生成和新生血管的形成,抑制肿瘤的生长。Objective To observe the effect of HIF-la antisense oligonucleotide （HIF-1α ASOND） on implanted human gastric cancer in nude mice. Methods BALB/c nude mice were subcutaneously transplanted with SCG-7901 tumor cells, then the mice were randomly divided into antisense oligonucleotide （ASOND） group, sense oligonucleotide （SOND） group and the control group. The HIF-la ASOND complexed with cationic liposome, HIF-1α SOND complexed with cationic liposome and liposome were injected intra-tumorally in the above groups, respectively. Tumor growth curve in each group animals was observed. The tumor weight was measured and then the rate of inhibition was calculated. The morphological changes of tumor cells was observed under microscope. The expression of HIF-1α, VEGF and MVD in tumor tissue was determined by immunohistochemical methods. Results The growth of tumorof ASOND group was significantly inhibited. There was statistically significant difference （P〈 0.05） in the weight of tumor between ASOND group and control group. The inhibitory rates of ASOND group and SOND group were 47.94% and 16.88% respectively, and both inhibitory rates were significantly different （P〈 0.01）. The tumor tissue expression of HIF-1α, VEGF and MVD in ASOND group was significantly lower than those of SOND and the control groups （P〈0. 01）. Conclusion In tumor tissue, the injection of HIF-1α ASOND to treat gastric carcinoma transplanted subcutaneously in nude mice can reduce the expression of HIF-1α, consequently reduce the formation of VEGF and new blood vessels, so as to achieve inhibition of tumor growth.

关 键 词：反义寡核苷酸 缺氧诱导因子-1Α 基因治疗 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]