Objective To investigate the inhibitive effect of HSV-tk/GCV system combining with ginsenosides on the growth of murine transplanted malignant melanoma, and to explore the synergistic effect of ginsenosides on HSV-tk/GCV system in treating murine transplanted malignant melanoma. Methods Eighty-five C57BL/6J male mice were used for the experiment. Of them, 5 mice were in the normal control group, the other mice were inoculated subcutaneously with the mixed cells of B16/tk and B16 wild type in the proportion of 1: 4. Each mice was inoculated 0. lmL (2 × 106 cells/mL) of the mixed cells probably. When the tumor could be touched, the tumor-bearing mice were divided into four groups randomly: model group, GCV treated group, ginsenosides treated group and GCV/ginsenosides combination group. The medication groups were given the corresponding drugs intraperitoneally for 7 continuous days. After treatment, the tumor mass weight was examined, tumor-inhibition rate was counted, and the routine pathological examination was performed. B16tk cells as well as the mixed cells of 20％ B16tk+ and tk were cultured with various concentrations of ginsenosides alone or combining with ganciclovir (GCV), and then the survival rate in different groups was examined by methyl thiazolyl tetrazolium (MTT) assay. The synergistic effect of ginsenosides on HSV-tk/GCV system in treating B16 cells was evaluated by q value analysis. Results Tumor mass weight was less in the medication groups than that in the model group. The combination group had the highest tumor-inhibition rate (32. 29％ ), and the difference was significant compared with that in the model group (P ＜ 0. 05 ). GCV treated group and ginsenoside treated group had higher tumorinhibition rate, but the difference was insignificant compared with that in the model group ( P ＞ 0. 05 ). The result of MTT assay indicated that the inhibitive effect of ginsenoside alone on B16 cells was not remarkable. The Kim Jung-kwan q values were less than 1.15 in the groups after culturing with ginsenoside combining with GCV for 72 hours. The results of pathological examination indicated that the infiltration of lymphocytes was obvious in ginsenosides groups and GCV/ginsenosides combination groups compared with that in the model group. Conclusion Ginsenosides can enhance the bystander effect of HSV-tk/GCV system in treating C57 murine transplanted malignant melanoma, and the synergistic mechanism is probably through the regulation of immunity.%[目的]观察人参总皂苷联合自杀基因HSV-tk/GCV治疗系统对小鼠黑色素瘤的生长抑制效应,探讨人参总皂苷对黑色素瘤自杀基因治疗的增效作用.[方法]选用85只C57BL/6J雄性小鼠,除正常组5只外其他均接种含20%B16tk+细胞的tk+和tk-混合细胞,造模成功后随机分为模型组、人参总皂苷组、tk/GCV组、人参总皂苷联合tk/GCV组(联合治疗组),每日腹腔注射给药,连续治疗7d后检测瘤块质量,计算抑瘤率并进行常规组织病理学检查.以不同浓度人参总皂苷与更昔洛韦(GCV)分别或共同作用于B16tk-细胞,以及含20% B16tk+细胞的tk+和tk-混合细胞,采用四甲基偶氮唑盐(MTT)法检测各组存活率,用金正均q值法分析人参总皂苷与自杀基因系统联合的相互作用是否具有协同性.[结果]各治疗组瘤块质量均较模型对照组低,联合治疗组的抑瘤率最高(32.29%),该组瘤体质量与模型组比较差异具有显著性意义(P＜0.05);人参总皂苷、tk/GCV组的抑瘤率次之,其瘤体质量与模型组比较差异无显著性意义(P>0.05);MTT检测结果显示:单独人参总皂苷对B16细胞的抑制程度不高,各浓度人参总皂苷联合tk/GCV作用72h所得的金正均q值均小于1.15;肿瘤组织的病理切片结果显示人参总皂苷组和联合治疗组的淋巴细胞浸润程度明显高于模型组.[结论]人参总皂苷能够提高自杀基因系统对黑色素移植瘤的旁杀伤效应,其增效机制可能是通过机体的免疫调节途径实现.
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