格尔德霉素在体内外增强人乳腺癌对阿霉素的敏感度

doi:10.3971/j.issn.1000-8578.2010.10.004

格尔德霉素在体内外增强人乳腺癌对阿霉素的敏感度

Geldanamycin Sensitizes Human Breast Cancer Cells to Adriamycin both in vitro and in vivo

摘要

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。

Abstract: 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%,P＜0.01) and induced apoptosis (Apoptosis rate 42.97±4.1%,P＜0.05). Tumor growth was also inhibited in vivo (68±9.4%,P＜0.05). TUNEL assay revealed that combined treatment of GA and ADM induced increased apoptosis (14.7±3.3%,P＜0.01). Conclusion GA sensitized human breast cancer MCF-7 cells to ADM, and GA+ADM thus was a promising combination for breast caner treatment.

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