靶向性自杀基因治疗系统联合放射线治疗前列腺癌移植瘤的实验研究

The study of irradiation combined with targeted suicide gene therapy for prostate cancer xenografts

目的初步判断针对整合素αv的靶向性自杀基因治疗系统（RGD-4C AAVP HSV-TK／GCV）是否能提高前列腺癌细胞株DU145移植瘤的放射效应。方法建立移植性前列腺癌细胞株DU145的裸鼠肿瘤模型48只。当位于每只裸鼠右大腿的肿瘤直径达6．0mm（5．8-6．3mm）时，开始实验。实验共分成6组（每组8只），分别为对照组、单纯放射组、单纯RGD-4C AAVP HSV-TK／GCV组（RGD-4C组）、单纯AAVP HSV-TK／GCV组（无RGD-4C组）、RGD-4C AAVP HSV-TK／GCV联合放射组（XRT＋RGD-4C组）和AAVP HSV-TK／GCV联合放射组（XRT＋无RGD-4C组）。观察指标为肿瘤生长延迟时间（肿瘤从6．0mm生长至12．0mm所需时间）和肿瘤治愈情况。结果除5只在实验过程中死亡外，单纯放射组、RGD-4C组、无RGD-4C组各有1只和XRT＋RGD-4C组3只肿瘤被治愈。统计分析余下37只肿瘤生长情况发现，RGD-4C组、无RGD-4C组和单纯放射组的绝对延迟时间分别为（24．4±9．0）、（22．6±11．3）和（28．3±5．5）d；当RGD-4C AAVP HSV-TK／GGV和AAVP HSV-TK／GCV分别联合放射时，其绝对延迟时间分别为（64．7±23．8）和（35．4士9．6）d，而标准化的延迟时间则分别为（40．3±23．8）和（12．8±9．6）d，它们对放射的增益因子分别为1．42和0．45。结论针对整合素αv的靶向性自杀基因治疗系统RGD-4C AAVP HSV-TK／GCV能显著提高前列腺癌细胞株DU145移植瘤的放射效应，值得进一步研究。

Objective To study whether RGD-4C AAVP HSV-TK/GCV, one of suicide gene therapy targeting to Integrin cry, can enhance radiotherapeutic effect for DU145 prostate cancer xenografts or not. Methods When the diameter of tumor in 48 nude mice bearing DU145 prostate cancer in the right leg attained 6.0 mm （5.8 - 6.3 ram）, the mice were entered into the experiment. There were 6 experimental groups （8 mice per group）, including the control, radiotherapy only （RT）, RGD-4C AAVP HSV-TK/GCV only （Targeted, RGD.4C）, AAVP HSV-TK/GCV （Non-targeted, non RGD-4C）, radiotherapy plus RGD-4C AAVP HSV-TK/GCV（XRT ＋ RGD-4C） and radiotherapy plus AAVP HSV-TK/GCV group （XRT ＋ Non RGD-4C ）. The effect of treatment was assessed by tumor growth delay （the time required when tumor grew from 6.0 mm to 12.0 mm） and tumor cure. Results Five mice died during the treatment course. There were 6 mice without tumor after treatment, including 1 in RT group, 1 in RGD-4C group, 1 in non RGD-4C group and 3 in XRT ＋ RGD-4C group, respectively. For tumor growth delay analysis in 37 mice, the absolute growth delay （AGD） for RGD-4C, non RGD-4C and RT group was 24.4 ± 9.0,22.6 ± 11.3 and 28.3 ± 5.5 days, respectively. When RGD-4C AAVP HSV-TK/GCV or AAVP HSV-TK/GCV combined with radiotherapy, their AGD was 64.7 ±23.8 and 35.4 ±9.6 days, and nominal growth delay （NGD） was 40.3 ±23.8 and 12.8 ±9.6 days, respectively. The enhancement factor of RGD-4C AAVP HSV-TK/GCV and AAVP HSV-TK/GCV for radiotherapy were 1.42 and 0.45. Condusion RGD-4C AAVP HSV-TK/GCV can enhance radiotherapeutic effect for DU145 prostate cancer xenografts. Further study is needed.