hTR-siRNA腺病毒对裸鼠人宫颈癌移植瘤的治疗作用  

Therapeutic Effects of hTR-siRNA Adenovirus on Human Cervical Cancer Xenografts in Nude Mice

作　　者：李婉宜[1] 李明远[1] 肖丽英[2] 张朝良[2] 刘豫蓉[2] 李小玉[2] 张思源[1] 李燕[2] 

机构地区：[1]四川大学华西基础医学与法医学院微生物学教研室,成都610041 [2]四川大学口腔疾病研究国家重点实验室

出　　处：《四川大学学报（医学版）》2008年第5期711-714,731,共5页Journal of Sichuan University(Medical Sciences)

基　　金：教育部博士点基金(20040610050)资助

摘　　要：目的探讨人端粒酶RNA(hTR)-siRNA腺病毒对裸鼠人宫颈癌移植瘤的治疗作用及其机制。方法将HeLa细胞注射到裸鼠的右腋皮下建立肿瘤模型,27d后将荷瘤裸鼠随机分为4组,采用瘤体内多点注射方式,分别向各组荷瘤鼠注射0.1mL的DMEM、Ad-NT-siRNA(1013pfu/L)、Ad-hTR-siRNA(1013pfu/L)或顺铂(1.20g/L),以后每隔3d注射1次,连续15d。观察注射腺病毒后移植瘤的体积变化、毒副作用。治疗结束后间隔7d处死动物,剥离出肿瘤组织称重。切取瘤组织做TUNEL染色测定组织的凋亡指数。结果将HeLa细胞移植到裸鼠皮下,成瘤率为100%。与Ad-NT-siRNA处理组相比,Ad-hTR-siRNA处理组的裸鼠移植瘤的体积和质量分别降低45.48%和34.68%,TUNEL分析显示凋亡细胞量约11.8%;但是Ad-hTR-siRNA的抗肿瘤作用不及顺铂。结论hTR-siRNA腺病毒能够明显抑制裸鼠人宫颈癌移植瘤的生长,其抗肿瘤机制与诱导肿瘤细胞凋亡、坏死有关。Objective To study the anti-tumor effects and its mechanism of hTR-siRNA adenovirus on human cervical cancer in vivo. Methods The in vivo model of human cervical cancer was established by the subcutaneous inoculation of HeLa cells at the right armpit of BALB/e nu/nu mice. After successful implantation, the mice were randomized into four groups, in which the mice were intratumorally injected with 0. 1 mL of Ad- hTR-siRNA （10is pfu/L）,or Ad-NT-siRNA （1013 pfu/L）, or Cisplatin （1. 20 g/L）, or serum-free DMEM alone respectively. These treatments were given once every 3 days for 6 times. After the last injection, the mice were observed for 7 days continuously and sacrificed at the end. The tumors were harvasted, weighed, and sectioned. The TUNEL assay was used to assess the apoptosis of these tumor cells. Results Tumors-implanted were established successfully by 100% with HeLa cells. As compared with Ad-NT-siRNA, Ad-hTR-siRNA could slow down tumor growth, decrease tumor volume （45. 48%） and tumor weight （34. 68%）, as well as promote the apoptosls and necrosis of tumor cells. The TUNEL positive ceils were about 11.8%. But the anti-tumor activity of Ad-hTR-siRNA didn＇t catch on Cisplatin＇s. Conclusion This study indicated that the hTR-siRNA adenovirus could suppress cervical cancer-xenografted growth in vivo and induce tumor cell apoptosis or necrosis.

关 键 词：宫颈癌 腺病毒 RNA干扰 HTR基因 

分 类 号：R737.33[医药卫生—肿瘤]