HSV-TK/GCV自杀基因系统联合γ射线放射治疗宫颈癌的实验研究

目的 探讨HSV-TK／GCV自杀基因系统协同^60Coγ射线放射治疗对人宫颈癌细胞系的体内外联合杀伤作用，以及HSV-TK／GCV对放射治疗的增敏作用。方法 分别以HSV-TK／GCV、^60Coγ射线放射治疗及两者联合治疗人宫颈癌HeLa细胞系和裸鼠宫颈癌移植瘤模型，比较治疗效果；利用增敏效应比值（E／O）、克隆形成实验评价体内外HSV-TK／GCV对放射敏感性的影响。结果 在体外实验中，自杀基因对宫颈癌HeLa细胞生长的抑制率为45．8％，单纯放疗的抑制率为42．4％，而基因治疗与放疗联用的抑制率为87．5％，与前两者比较，差异有统计学意义（P〈0．01）；且联合治疗组对射线敏感性较单独治疗组明显增加，克隆形成率明显下降（P〈0．05）；在体内实验中，单纯基因治疗与放疗对HeLa细胞裸鼠皮下移植瘤生长的抑瘤率分别为39．5％和35．8％，而基因治疗放疗联用的抑瘤率达到87．9％，与前两者比较，差异均有统计学意义（P〈0．01）；增敏效应比值（E／O）为3．2（〉1．4），提示HSV-TK／GCV对放疗具有增敏作用。结论 HSV-TK／GCV自杀基因系统具有放射增敏作用，二者联合治疗可作为宫颈癌综合治疗的有效补充方法。

In vivo and in vitro experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and 60Co radiotherapy

Objective To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with ~(60)Co radiotherapy on human cervical cancer HeLa cell line in vivo and in vitro, and to explore radiosensitization by the HSV-TK/GCV system. Methods The HSV-TK/GCV suicide gene therapy system and ~(60)Co radiotherapy were used separately or in combination for human cervical cancer HeLa cell line in vivo and in vitro to compare their effects.Colony formation test and the rate of radiosensitization effect(E/O)were employed to observed the radiosensitization by the HSV-TK/GCV system. Results The HSV-TK/GCV suicide gene therapy system showed strong therapeutic effects on HeLa cells both in vitro and in vivo(the inhibition rates were 45.8% and 39.5%,respectively).Moreover,the combined application of gene therapy and radiotherapy exhibited stronger therapeutic effects in vitro and in vivo(the inhibition rate was 87.5% in vitro,and was 87.9% in vivo)(P<0.01).The inhibition rate of radiotherapy alone was 42.4% in vitro and 35.8% in vivo.The sensitivity to radiotherapy in combined therapy increased more than that of either therapy alone,and the ability of colony formation decreased(P<0.01).The rate of radiosensitization effect(E/O)was 3.2(>1.4),indicating the HSV-TK/GCV system could exert a sensitizing effect on ~(60)Co radiotherapy of the transplanted human cervical cancer cells in nude mice. Conclusion The HSV-TK/GCV system has radiosensitizationaction.Gene therapy combined with radiotherapy may be a good supplementary method for synthetic treatment of cervical cancer.