Survivin反义寡核苷酸抑制肝癌裸鼠皮下移植瘤生长的作用

目的：研究survivin反义寡核苷酸（ASODN）对人肝癌耐药细胞株移植裸鼠皮下后，移植瘤生长的抑制作用。方法:将人肝癌耐药细胞系SMMC-7721/ADM裸鼠移植瘤模型，随机分为：空白对照组、单纯脂质体转染组、正义链转染组、200 μg/L ASODN组、400 μg/L ASODN组和600 μg/L ASODN组，观察裸鼠移植瘤体积，计算抑瘤率。免疫组化检测Survivin蛋白的表达。结果:A组、B组和C组移植瘤随时间增长而增大，但3组间无显著差异（P>0.05）。D组、E组和F组注射ASODN后，裸小鼠移植瘤的体积随着注射ASODN时间的延长和ASODN浓度的增加，移植瘤生长越来越小，并呈时间-剂量-效应依赖性。实险第20 d D组、E组和F组的肿瘤抑制明显大于A组、B组和C组（P<0.05）。HE染色见对照组移植瘤细胞密集成群，核大深染，而ASODN组见肿瘤细胞少，癌细胞皱缩变圆，胞核固缩深染。免疫组化见对照组肝癌细胞浆Survivin蛋白表达较强，而ASODN组Survivin蛋白表达较弱。结论:Survivin反义寡核苷酸能够抑制裸鼠皮下移植瘤的生长。

Inhibitory effect of liposomes survivin antisense oligonucleotide on human hepatic carcinoma transplanted subcutaneously in nude mice

AIM: To explore the effects of liposomes survivin antisense oligonucleotides (ASODN) on growth of human hepatic carcinoma transplanted subcutaneously in nude mice. METHODS: Nude mouse model of human hepatic cancer was established by transplantation of hepatic cancer cell line SMMC-7721/ADM subcutaneously. Models were divided randomly into six groups: control group, liposome group, sense oligonucleotide (SODN) group, 200 μg/L, 400 μg/L and 600 μg/L ASODN groups. Different treatments were given respectively. Weight and volume of subcutaneous tumors were measured, and tumor growth inhibitory rate was calculated. Morphological changes of transplanted tumor cells were observed under light microscope. The expression of Survivin was detected by immunohistochemistry. RESULTS: The growth of tumors was significantly inhibits in all ASODN groups compared with control, liposome and SODN groups (P<0.05). Volume of subcutaneous tumors decreased in a time-dependent and dosage-dependent manner (P<0.5). CONCLUSION: Survivin ASODN inhibits the growth of human hepatic carcinoma in nude mice.