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目的 研究格尔德霉素 (Geldanamycin ,GDM)对人肝癌BEL 74 0 2细胞周期的影响及顺铂和丝裂霉素C等药物联用GDM后的体外体内抗肿瘤作用。方法 用MTT法检测药物对肝癌BEL 74 0 2细胞的生长抑制作用 ;流式细胞术分析细胞周期 ;小鼠移植性肝癌 2 2模型研究药物的体内抗肿瘤作用。结果 MTT法测得GDM对BEL 74 0 2细胞的生长抑制作用IC50 为 0 2 8μmol·L-1。GDM 0 1,1 0和 10 μmol·L-1处理BEL 74 0 2细胞 ,引起S期细胞比例下降和G2 M期的明显阻断。在较低浓度 ,GDM 0 1μmol·L-1和 0 2 μmol·L-1均增强一系列化疗药物包括顺铂、丝裂霉素C、阿霉素和阿糖胞苷对BEL 74 0 2细胞的细胞毒作用。小鼠移植肝癌 2 2模型中 ,GDM 0 38mg·kg-1增强顺铂和丝裂霉素C的抗肿瘤作用。协同作用十分显著 ,CDI <0 7。结论 这些结果提示GDM作为以抑制热休克蛋白 90 (Hsp90 )功能为靶点的生化调节剂可能应用于肿瘤联合化疗的前景
Objective To study the effect of geldanamycin (GDM) on the cell cycle of human hepatocellular carcinoma BEL-7402 cells and the in vitro antitumor effect of GDM combined with cisplatin and mitomycin C in vitro. Methods MTT assay was used to detect the growth inhibition of hepatocellular carcinoma BEL 74 0 2 cells. Flow cytometry was used to analyze the cell cycle. The transplanted hepatocellular carcinoma 2 2 model was used to study the antitumor activity of the drug in vivo. Results The IC50 of GDM on BEL 74 0 2 cells was 0 2 8 μmol·L-1. GDM 0,1 0 and 10 μmol·L-1 treatment BEL 74 0 2 cells, causing a decline in the proportion of S-phase cells and G2 M phase of the significant block. At lower concentrations, GDM 0 1 μmol·L-1 and 0 2 μmol·L-1 enhanced a number of chemotherapeutic drugs including cisplatin, mitomycin C, doxorubicin and cytarabine on BEL 74 0 2 cells Cytotoxicity. Mice transplantation of hepatocellular carcinoma 2 2 model, GDM 0 38mg · kg-1 enhanced cisplatin and mitomycin C anti-tumor effect. Synergy is very significant, CDI <0 7. Conclusions These results suggest that GDM as a biochemical regulator that targets the inhibition of Hsp90 function may be used in the future of combination chemotherapy of tumors