雷公藤红素对紫杉醇耐药乳腺癌细胞生长的抑制作用  

Inhibitory effect of celastrol on the growth of taxol-resistant breast cancer cells

作　　者：谢闺娥[1,2] 杜晶春[1] 徐霞[1] 

机构地区：[1]广州医科大学金域检验学院,广东广州510182 [2]广州医科大学附属广州市妇女儿童医疗中心,广东广州510623

出　　处：《广东药学院学报》2016年第3期335-338,共4页Academic Journal of Guangdong College of Pharmacy

基　　金：国家自然科学基金项目(81101682);广东省公益研究与能力建设专项资金项目(2014A020212015)

摘　　要：目的研究雷公藤红素对紫杉醇耐药乳腺癌细胞生长的作用及其机制。方法用MTT法检测雷公藤红素对紫杉醇耐药MCF-7/TAX细胞生长的影响;Annexin V-FITC/PI染色检测雷公藤红素对MCF-7/TAX凋亡的诱导作用;Caspase酶活性测定分析雷公藤红素作用后,MCF-7/TAX细胞中Caspase-8、-9活化程度。结果 MCF-7/TAX对紫杉醇耐药指数达19.39;而雷公藤红素对MCF-7/TAX细胞的生长有高效抑制作用,且呈现明显的剂量依赖性,对其作用48 h的IC50为0.92μmol/L,MCF-7/TAX对雷公藤红素的敏感性高于MCF-7,耐药指数仅为0.77。雷公藤红素作用后,Annexin V染色阳性的MCF-7/TAX细胞较对照明显升高。Caspase酶活性测定结果显示,雷公藤红素作用24 h后,MCF-7/TAX细胞中Caspase-8、-9酶活性均显著升高。结论雷公藤红素能同时激活内外源性凋亡途径,诱导MCF-7/TAX细胞凋亡的发生,从而高效抑制紫杉醇耐药MCF-7/TAX乳腺癌细胞的生长。Objective To investigate the effect of celastrol on the growth of taxol-resistant breast cancer cells and explore its underlying mechanism. Methods After treatment with celastrol, the growth of taxol-resistant MCF-7/TAX cells was analyzed by MTT assay, the cell apoptosis was evaluated by Annexin V-FITC/PI staining, and the activity of Caspase-8 and -9 was quantified by enzymatic activity assay. Results Treatment with celastrol markedly inhibited MCF-7/TAX cell growth in a dose-dependent manner, and its ICs0 was 0.92 p, mol/L. Celastrol decreased the resistance index of MCF-7/TAX cells from 19.39 to 0.77. Celastrol treatment facilitated the cell apoptosis and increased the activities of Caspase-9 and -8 in MCF-7/TAX cells. Conclusion Celastrol may suppress the growth of taxol-resistant MCF-7/TAX cells by up-regulation of both intrinsic and extrinsic apoptotic pathways.

关 键 词：紫杉醇耐药 雷公藤红素 MCF-7/TAX 凋亡 

分 类 号：R285[医药卫生—中药学]