重组IFN-α2a与HSV-tk/GCV系统协同作用增强对于卵巢癌细胞系SKOV3杀伤作用的体外研究  

Recombinant Interferon α2a Synergistically Enhances SKOV3 Ovarian Tumor Cell Killing by the HSV-tk/GCV System

作　　者：程月鹃[1] 潘凌亚[1] 张毅[2] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院妇产科,北京100730 [2]军事医学科学院基础医学研究所,北京100850

出　　处：《中国肿瘤生物治疗杂志》2001年第1期13-16,共4页Chinese Journal of Cancer Biotherapy

摘　　要：目的 :观察应用重组IFN α2a能否增强单纯疱疹病毒胸腺嘧啶核苷激酶基因 (HSV tk) /丙氧鸟苷 (GCV)系统对卵巢癌细胞系SKOV3的杀伤效应。方法 :利用逆转录病毒载体将潮霉素磷酸转移酶和HSV tk的融合基因 (hytk)导入SKOV3细胞 ,测定GCV对SKOV3/hytk细胞的杀伤作用和旁观者效应。观察IFN α2a与HSV tk/GCV协同作用对旁观者效应的影响 ,并且在联合应用GCV和IFN α2a后 ,进行细胞周期分析。结果 :GCV对SKOV3/hytk细胞有明显的杀伤作用 ,并且可以同时杀伤周围未转基因的细胞 ,联合应用IFN α2a与HSV tk/GCV可以明显增强旁观者效应 (P <0 .0 5 ) ,使处于S期的SKOV3/hytk细胞较对照组和使用单药组明显增多 (P <0 .0 1)。结论 :IFN α2a与HSV tk/GCV联合应用可以产生协同作用 ,增强HSV tk/GCV系统在体外对卵巢癌细胞系SKOV3的杀伤效应 。Objective: To determine if IFN-α2a and HSV-tk/GCV have synergy on the cell killing of the SKOV3 human ovarian tumor cell line. Methods: hytk gene retroviral vector plasmid was transduced into SKOV3 cells. Both the cytotoxicity and the bystander effect were evaluated after the treatment of GCV. IFN-α2a and HSV-tk/GCV were used together to determine if they have synergy on the tumor cell killing effect, then post-treatment cell cycle analysis was carried out.Results: A dose dependent cell killing of SKOV3/hytk was observed after treatment with GCV. Bystander effect was seen in mixed culture of hytk-positive and -negative cells. Furthermore, IFN-α2a had a significant (P<0.05) synergistic effect on the growth inhibition of the same mixture of modified and unmodified SKOV3 cells in combination with HSV-tk/GCV system. Cell cycle analysis has shown that treatment with IFN-α2a and HSV-tk/GCV caused an increase(P<0.01) in cells in S phase 24 hours after therapy in the HSV-tk expressing cells. Conclusion: IFN-α2a enhances the GCV mediated killing of HSV-tk expressing cells and nearby unmodified cells in a synergistic manner in vitro. This finding suggested that IFN-α2a might be a useful adjunctive therapy for the HSV-tk/GCV system.

关 键 词：卵巢癌 HSV-TK/GCV IFN-Α2A 

分 类 号：R737.31[医药卫生—肿瘤]