ATRA联合HSV1-TK/GCV系统治疗卵巢癌的实验研究  

Experimental Study of the Combination of ATRA and HSV1-TK/GCV for Ovarian Cancer

作　　者：徐梅[1] 吴强[2] 谢永[1] 朱孝荣[3] 

机构地区：[1]徐州市中心医院妇产科,221000 [2]江苏省肿瘤医院妇瘤科,210009 [3]徐州医学院动物中心,221000

出　　处：《实用癌症杂志》2007年第2期111-114,共4页The Practical Journal of Cancer

基　　金：江苏省科技厅社会发展资助项目

摘　　要：目的探讨全反式维甲酸(all-trans retinoic acid,ATRA)能否提高Ⅰ型单纯疱疹病毒胸苷激酶(herpes simplex virus thymidine kinase,HSV1-TK)/丙氧鸟苷(ganciclovir,GCV)系统对卵巢癌的体内治疗作用。方法用携带tk基因的重组逆转录病毒上清转染人卵巢癌细胞系SKOV-3,用含G418的培养液筛选获得抗性克隆(命名为SKOV-3/TK)。采用PCR方法检测HSV1-tk基因整合情况。分别用SKOV-3细胞建立皮下移植瘤裸鼠模型作为对照组和ATRA组,用SKOV-3细胞与SKOV-3/TK细胞按8∶2比例混合细胞建立的动物模型作为HSV1-tk/GCV组和HSV1-tk/GCV联合AT-RA组。于接种细胞后15天开始实验用药,从用药第1天开始每5天测量肿瘤体积1次,至用药结束后2周,绘制肿瘤生长曲线,计算抑瘤率,并取瘤组织做病理学检查。结果与对照组比较,ATRA组、HSV1-tk/GCV组抑瘤率分别为25.5%、38.8%,联合用药组抑瘤率高达67.8%,有统计学意义,P<0.05。病理结果显示实验组出现不同程度点、片状坏死,以联合用药组为重。结论HSV1-TK/GCV系统对卵巢癌有体内杀伤作用;ARTA可以提高HSV1-TK/GCV系统对卵巢癌的体内杀伤作用。Objective In order to study whether All-trans retinoie acid （ATRA） could enhance the killing effect of a suicide gene therapy system of HSVI-tk/GCV （ herpes simplex type I virus thymidine kinase / ganciclovir ） for ovarian cancer in vivo. Methods Human ovarian cancer cell line SKOV-3 was transfected with the recombinant retrovirus, containing HSVI-tk gene. Following selection by G418 medium, resistant clones （named SKOV-3/TK ） were identified by PC R. Subcutaneous tumor models were induced in nude mice by injection with different cells. Nude mice subcutaneous injection with SKOV-3 cells were used as blank control and ATRA group. Those subcutaneous injection with the mixture of 80% SKOV-3 cells and 20% SKOV-3/ TK cells were used as HSVI-tk/GCV group and ATRA combined with HSVI-tk/GCV group. Experimental administration after cells injection 15 days. The average tumor volume were examined, the rates of tumor grouth inhibition were calculated, and the curve of the tumer volume were drawn. The tumors were removed for histopathological analysis. Results Compared with control group,tumor growth inhibition rate of ARTA,HSV1-tk/GCV and the combination group was 25.5% ,38.8% and 67.8% respectively. Which were significant different, P 〈 0.05. The extensive necrosis were observed in the treated mice of the combination therapy group. Condusion HSVI-tk/GCV suicide gene therapy system has a powerful killing effect for ovarian cancer in vivo, and a synergistic anticancer effect was observed when combined with ARTA.

关 键 词：全反式维甲酸 单纯疱疹病毒胸苷激酶(HSV-TK) 卵巢癌 

分 类 号：R737.31[医药卫生—肿瘤]