生存素反义核酸联合泰素帝治疗荷耐药结肠癌移植瘤裸鼠的初步观察

Inhibitory Effect of Antisense RNA Targeting survivin Gene Combined with Taxotere on Transplanted Multidrug Resistant Colorectal Carcinoma in Nude Mice

目的探讨生存素(survivin)反义基因与化疗联合应用提高耐药结肠癌疗效的可行性。方法以泰素帝、survivin反义核酸及survivin反义核酸联合泰素帝分别对荷LoVo/Adr结肠癌鼠模型进行干预治疗,观察肿瘤生长情况,并检测肿瘤组织survivin蛋白表达变化及凋亡变化。结果单用泰素帝对LoVo/Adr移植瘤无明显抑制作用,survivin反义核酸能有效抑制移植瘤生长,survivin反义核酸联合泰素帝对肿瘤抑制作用最明显。泰素帝对肿瘤组织survivin蛋白表达无明显影响,survivin反义核酸能显著降低肿瘤组织survivin蛋白的表达,survivin反义核酸联合泰素帝对肿瘤组织survivin蛋白降低作用最为明显。各组肿瘤组织凋亡指数分别为(7.0±1.83)%、(21.50±2.38)%和(43.5±3.87)%,前者与对照组(6.5±1.29)%相比差异无统计学意义(P>0.05),后两者与对照组比较差异有统计学意义(P<0.01)。结论survivin反义核酸对泰素帝具有明显增效作用,两者联合应用能发挥对耐药结肠癌的协同治疗效应。

Objective To investigate the anti-tumor effect of an antisense RNA eukaryotic expression plasmid pcDNA3. 0/survivin targeting survivin gene combined with taxotere on multiple drug resistant （MDR） colorectal carcinoma in vivo. Methods Human colorectal carcinoma model of nude mice were given the following treatment, taxotere, antisense survivin RNA, and antisense survivin RNA combined with taxotere, respectively. Tumor growth inhibitary rates were calculated when the mice were killed 4 weeks later. The survivin protein expression was detected by immunohistochemistry method and tumor apoptosis was analyzed by TUNEL assay. Results Taxotere bad no therapeutic effect on transplanted colorectal tumor. Antisense survivin RNA could down-regulate survivin protein expression in tumor tissue, and taxotere didn＇t have the same effect. When treated with antisense survivin RNA and taxotere, tumor tissue survivin protein decreased most obviously. Apoptosis index （AI） was （7.0 ± 1.83）%, （21.50±2.38） % and （43.5 ±3.87）% respectively in the three groups above. AI in the former group had no statistical significance compared with the control group（P〉0. 05）, and that in the latter two groups were significantly higher than the control group（P〈0. 01）. Conclusion The antisense survivin RNA could enhance the chemosensitivity of colorectal carcinoma to taxotere.