腺病毒介导胸苷激酶基因联合α-IFN治疗肾癌的实验研究

Adenovirus-mediated TK gene combined with α-IFN in treatment of nude mice transplanted with human renal clear-cell carcinoma

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(50mg/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。

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 α- gainst 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. Resuits： The survival rate of 786-0 cells was （35.07＋1.43）% in the TK＋GCV＋ α-IFN group, （68.57：1： 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.