摘要
研究抗生素苯醌安莎霉素(Geldanamycin ,GDM)对人肝癌BEL 7402细胞周期的影响和联合应用顺铂 (CDDP)的体外体内抗肿瘤作用。方法 :采用MTT法检测药物的生长抑制作用 ,[3H] TdR掺入法测定DNA合成抑制作用 ,流式细胞术分析细胞周期 ,小鼠移植性肝癌H22模型研究药物单用或联合应用时的体内抗肿瘤作用。结果 :MTT法测得GDM对BEL 7402细胞的生长抑制IC50为0 28μmol/L。GDM处理BEL 7402细胞4h ,抑制DNA合成的IC50为14μmol/L。1 0、10μmol/LGDM处理BEL 7402细胞24h后S期细胞比例明显下降 ,并持续到48h ;0 1、1 0、10μmol/L的GDM引起G2/M期的明显阻断 ,24h时达高峰值 ,48h后开始回复。体外0 1μmol/L和0 2μmol/LGDM均增强CDDP对BEL 7402细胞的细胞毒作用。小鼠移植肝癌H22模型中 ,单用1 5mg/kgCDDP组两批试验的抑瘤率均为73 % ,顺铂联用0 38mg/kgGDM两批试验的抑瘤率分别为89 %和82% ,两者有显著性差异(P<0 05) ,其CDI值分别为0 41和0 72。结论
Objectives: To study the effect of antibiotic geldanamycin on cell cycle of human hepatoma BEL 7402 cells and the antitumor activityof cisplatin by combination with geldanamycin in vitro and in vivo Methods: MTT assay was used to determine the growth inhibition of hepatoma BEL 7402 cells by the drugs Effect of geldanamycin on DNA synthesis was tested by TdR incorporation assay Cell cycle was analyzed by flow cytometry Transplantable murine hepatoma 22 model was used to evaluate the antitumor activity of drugsin vivo Results: The IC50 value of geldanamycin for hepatoma BEL 7402 cellsby MTT assay was 0 28 μmol/L Geldanamycin inhibited DNA synthesis As the cells exposed to the drug for 4 h, the IC50 value was 14 0 μmol/L At concentrations of 0 1,1 0,and 10 μmol/L, geldanamycin delayed the G1/S transition andinduced G2/M block in BEL 7402 cells At relatively low cytotoxic concentration, 0 1 or 0 2 μmol/L, geldanamycin markedly enhanced the cytotoxity of cisplatin against BEL 7402 cells The enhanced inhibition of tumor growth by cisplatin was also observed in hepatoma 22 bearing mice when cisplatin was administered by combination with 0 38 mg/kg geldanamycin The synergistic effects were very significant with CDI< 0 7 Conclusion: These results suggest that geldanamycin, as a biochemical modulator to enhance the therapeutic effects of cisplatin, may be potentially useful in cancer chemotherapy
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2000年第8期731-734,共4页
Chinese Journal of Cancer
基金
国家重点基础研究发展规划973项目!(编号G1988051200)
关键词
GELDANAMYCIN
顺铂
肿瘤
药物疗法
Geldanamycin/Therapeutic use
Cisplatin/Therapeutic use
Neoplasms/Drug therapy
Experimentalchemotherapy
