携带lipocalin2基因溶瘤腺病毒治疗结肠癌移植瘤的实验研究

Oncolytic adenovirus expressing lipocalin 2 suppresses the growth of transplantation tumors of colonic carcinoma

目的探讨携带lipocalin2基因的溶瘤腺病毒ZD55-lipocalin2对结肠癌移植瘤的治疗作用。方法选用SW620细胞构建结肠癌移植瘤模型，随机分为ZD-55组、Ad-lipocalin2组、ZD55-lipocalin2组及PBS对照组，瘤内注射相应病毒后观察移植瘤生长及裸鼠生存情况，计算移植瘤瘤重和抑瘤率。通过TUNEL调亡检测、免疫组化检测血管内皮细胞生成因子表达和微血管计数来观察ZD55-lipocalin2对大肠癌的抑制作用。结果ZD-55病毒组、Ad-lipocalin2病毒组和ZD55-lipocalin2病毒组抑瘤率分别为16．4％、18．9％、40．4％，凋亡指数分别为20．7％、19．3％、77．0％，微血管密度分别为34±6、30±6、11±4。ZD55-lipocalin2组与其他各组相比差异有统计学意义（P〈0．05）。结论ZD55-lipocalin2促进大肠癌细胞凋亡、抑制微血管生成，明显抑制大肠癌移植瘤生长。

Objective To investigate ihe antitumor activity of the oncolytic adenovirus expressing lipocalin 2 gene for colorectal cancer in vivo. Methods BALB/C nude mice subcutaneously inoculated by SW620 cells and grown tumors were treated with injection of ZD-55 virus, Ad-lipocalin 2 virus and ZD55- lipocalin 2 virus respectively. The weight of implanted tumors and the tumor inhibition rate were calculated to evaluate the anti-tumor effect. Cell apoptosis was determined by TUNEL and the protein expression of VEGF and MVD were determined with immunohistochemistry. Results ZD55-1ipocalin 2 inhibited the growth of transplanted tumor more significantly than ZD-55 virus and Ad-lipocalin 2 virus （P 〈 0. 05 ）. Tumor cell apoptosis was upregulated and the MVD reduced significantly in ZD55-1ipocalin 2 group in contrast to the other two groups （P 〈 0.05）. Conclusions ZD55-1ipocalin 2 induces apoptosis of colorectal tumor cells and inhibits tumor microvascular formation, slowing down the growth of transplantation tumors.