摘要
目的探讨新型抗肿瘤药物格尔德霉素(GA)联合阿霉素(ADM)治疗乳腺癌的机制。方法通过Western blot确定GA处理后AKT及HSP70表达变化,然后体外分别以GA/阿霉素(ADM)以及联合处理人乳腺癌MCF-7细胞,MTT法检测增殖变化,流式细胞仪检测细胞凋亡,在裸鼠模型体内检测GA联合ADM治疗后肿瘤大小变化并采用TUNEL法检测肿瘤细胞凋亡变化。结果 GA处理MCF-7细胞后AKT明显下降,HSP70无明显改变,GA联合ADM后,MCF-7细胞的增殖受到明显抑制,生存率为(51.90±6.80)%(P<0.01),凋亡明显增加,凋亡率为(42.97±4.10)%(P<0.05)。在裸鼠模型内肿瘤生长受到明显抑制,实验终点抑瘤率为(68.00±9.40)%(P<0.05),联合治疗明显增加瘤内肿瘤细胞的凋亡,凋亡率为(14.70±3.30)%(P<0.01)。结论 GA联合ADM能够显著增加ADM的治疗疗效,有望成为治疗乳腺癌的新型化疗联合方案。
Objective To explore effects of Geldanamycin（GA） combined with adriamycin（ADM） on human breast cancer cells.Method Human breast cancer MCF-7 cells were treated with GA,ADM and GA plus ADM,respectively.The expression of AKT and HSP70 was tested.MTT was used to test proliferation.Flow cytometer assay was performed to determine cellular apoptosis.Furthermore,MCF-7-bearing nude mice model was established and received different treatment.Tumor volume was measured.Apoptosis within tumor tissue was detected by a TUNEL assay.Results GA inhibited the expression of p-AKT but HSP70 in MCF-7 cells.Combination of GA and ADM significantly inhibited the proliferation of MCF-7 cells（Survival rate 51.9±6.8%,P0.01） and induced apoptosis（Apoptosis rate 42.97±4.1%,P0.05）.Tumor growth was also inhibited in vivo（68±9.4%,P0.05）.TUNEL assay revealed that combined treatment of GA and ADM induced increased apoptosis（14.7±3.3%,P0.01）.Conclusion GA sensitized human breast cancer MCF-7 cells to ADM,and GA＋ADM thus was a promising combination for breast caner treatment.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2010年第10期1109-1112,共4页
Cancer Research on Prevention and Treatment
关键词
乳腺癌
格尔德霉素
阿霉素
化疗敏感度
Breast cancer
Geldanamycin
Adriamycin
Sensitivity to chemotherapy
