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腺病毒介导胸苷激酶基因联合α-IFN治疗肾癌的实验研究
赵国志,郑少斌*,谭万龙,刘阳
0
(南方医科大学南方医院泌尿外科,广州 510515)
摘要:
目的:探讨腺病毒介导的单纯疱疹病毒1型胸苷激酶(TK)基因联合α-IFN对肾癌生长的抑制作用。方法:含TK基因的重组腺病毒感染人肾癌细胞株786-0,加用无环鸟苷(GCV) 或联用α-IFN,用噻唑蓝(MTT)方法观察杀伤效应。建立786-0裸鼠皮下移植瘤模型,瘤内注射腺病毒及腹腔注射GCV (50 mg/kg),联合α-IFN时行瘤内注射,用药后观察肿瘤生长情况。结果:在对感染腺病毒的786-0细胞的体外杀伤实验中,TK+GCV组的细胞存活率为(68.57±1.41)%,α-IFN组的细胞存活率为(68.65±1.45)%,TK+GCV+α-IFN组细胞存活率为(35.07±1.43)%( P=0.000),两者之间有协同效应。在786-0裸鼠移植瘤模型中,TK+GCV联合α-IFN能够显著抑制肿瘤的生长。结论:腺病毒为载体的自杀基因TK加前体药GCV联合α-IFN应用对人肾癌细胞的体内、外治疗效果明显。
关键词:  腺病毒载体  基因疗法  胸苷激酶基因  干扰素α  肾肿瘤
DOI:10.3724/SP.J.1008.2008.00294
投稿时间:2007-11-23修订日期:2008-02-07
基金项目:广东省医学科研基金(A20004395).
Adenovirus-mediated TK gene combined with α-IFN in treatment of nude mice transplanted with human renal clear-cell carcinoma
ZHAO Guo-zhi,ZHENG Shao-bin*,TAN Wan-long,LIU Yang
(Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China)
Abstract:
Objective:To investigate the inhibitory effect of adenovirus-mediated herpes simplex virus-thymidine kinase (TK) gene combined with α-IFN on renal clear-cell carcinoma. Methods: Adenovirus containing suicide gene TK, in combination with GCV or α-IFN, was used to treat human renal clear-cell carcinoma cell line 786-0, and the in vitro cytotoxic effects against 786-0 were evaluated using MTT method. The subcutaneous transplantation model of 786-0 cells was established with nude mice. Adenovirus containing TK gene was injected intratumorally and the GCV (50 mg/kg) was injected intraperitoneally; α-IFN (104 U/L) was injected intratumorally in combined therapy. The growth of tumors was observed after treatments. Results: The survival rate of 786-0 cells was (35.07±1.43)% in the TK+GCV+α-IFN group, (68.57±1.41)% in the TK+GCV group and (68.65±1.45)% in the α-IFN group ( P=0.000). There was an obvious synergic effect between Ad-TK and α-IFN in inhibiting 786-0 cells. Ad-TK combined with GCV and α-IFN significantly suppressed the growth of 786-0 cells growth in nude mice model.Conclusion: Adenovirus-mediated TK plus prodrug GCV combined with α-IFN has obvious therapeutic effect in treatment of human renal clear-cell carcinoma.
Key words:  adenovirus vector  gene therapy  thymidine kinase gene  interferon-α  kidney neoplasms