C-erbB-2与c-raf-1基因反义寡核苷酸联合对人卵巢癌裸鼠皮下移植瘤的治疗作用

背景与目的：针对c-erbB-2与c-raf-l单基因的反义寡脱氧核苷酸(antisense oligodexynucleotide,ASODN)治疗肿瘤的研究报道很多,这些研究往往局限于单个基因或细胞水平,从肿瘤发生的多基因学说上讲是不恰当的。本研究旨在探讨c—erbB-2与c-raf-1基因联合ASODN对人卵巢癌裸鼠皮下移植瘤的治疗作用。方法：在BALB／c裸鼠上建立卵巢上皮癌模型,然后随机分成阴性对照组和6个实验组(分别为脂质体c—erbB-2 SODN组、脂质体c-raf-l SODN组、脂质体c-erbB-2ASODN组、脂质体c-raf-l ASODN组、全剂量联合反义给药组、半剂量联合反义给药组)。检测裸鼠体重及肿瘤体积变化,计算抑瘤率及肿瘤缩小率。结果：给药后,全剂量联合反义给药组与半剂量联合反义给药组的肿瘤体积抑瘤率分别为72．5％和78．40%,肿瘤重量抑瘤率分别为70．7％和75．3％,肿瘤缩小率分别为29．7%和41．6％。在给药后,各组裸鼠体重变化无明显统计学差别。结论：C—erbB-2与c-raf-l基因联合ASODN在体内能明显地抑制肿瘤生长。

Therapeutic effects of C-erbB-2 and C-raf-1 gene combined with antisense oligodeoxynucleotide on the human ovarian carcinoma transplanted subcutaneously in nude mice

BACKGROUND & OBJECTIVE: Although many positive studies were reported on single C-erbB-2 or C-raf-1 antisense oligodeoxynucleo- tide (ASODN) in cancer treatment, these studies were usually limited in single gene or in cell level and were not appropriate according to the multiple genes hypotheses of tumorigenesis. This study was designed to investigate the effects of C-erbB-2 and C-raf-1 combined with ASODN on the treatment of ovarian carcinoma xenograft in nude mice. METHODS: The model of xenografts derived from ovarian epithelial cancer SKOV3 cells was established in Balb/C nude mice, then they were randomly divided into a negative control group and 6 experimental groups [intraperitoneal injection of (1)liposome-C-erbB-2-ASODN, (2)liposome- C-raf-1-ASODN, (3)liposome-C-erbB-2-ASODN, (4)liposome-C-raf-1-ASODN, (5)whole-dose combined ASODN, (6)half-dose combined ASODN. The weight of nude mice and tumor volume were measured. The tumor growth inhibitory rates and the tumor volume decreased rates were calculated. RESULTS: C-erbB-2 and C-raf-1 combined with ASODN exhibited potent tumor growth inhibition. The tumor volume inhibitory rates were 72.5% and 78.4%; the tumor weight inhibitory rates were 70.7% and 75.3%; the tumor volume decreased rates were 29.7% and 41.6% for whole-dose combined group and half-dose combined group post-experiment, respectively. Of the 7 groups, there was no significant difference on nude mice weight post-experiment and therefore the toxicity was endurable. CONCLUSION: C-erbB-2 and C-raf-1 combined with ASODN showed potent tumor growth inhibition in vivo.