目的探讨姜黄素联合阿霉素(adriamycin,ADM)对人乳腺癌MCF-7及MDA-MB-231细胞生长的影响及其作用机制。方法将体外培养的乳腺癌MCF-7及MDA-MB-231细胞处理不同浓度的姜黄素及ADM,MTT法检测细胞成活率,等效剂量法(Calcusy)分析联合指数,然后利用免疫印迹法检测PARP、Bcl-2、Bax及NF-κB(p65)蛋白表达水平。结果姜黄素和ADM两者合用可以协同抑制人乳腺癌MCF-7及MDA-MB-231细胞生长,其联合指数(ED50CI)分别为0.7和0.62。免疫印迹结果显示,联合给药可以明显增强MCF-7细胞PARP蛋白裂解,抑制Bcl-2蛋白表达,但对Bax蛋白表达无明显影响。联合用药可以抑制ADM诱导的NF-κB信号通路激活。结论姜黄素和ADM可能通过抑制ADM诱导的NF-κB激活继而促进肿瘤细胞凋亡来发挥协同的抗乳腺癌作用。
Abstract
Objective To investigate the anti-proliferative effect and underlying mechanisms of the combination of curcumin and adriamycin on breast cancer MCF-7 and MDA-MB-231 cells. Methods MTT was used to detect the cell viablility of MCF-7 and MDA-MB-231 cells after different concentrations of curcumin (Cur) and adriamycin(ADM) treatment. Calcusyn software was used for evaluating the combination index (CI). The proteins of PARP, Bcl-2, Bax, and NF-κB (p65) were detected by Western blotting. Results The combination of Cur and ADM synergisticly inhibited the growth of MCF-7 and MDA-MB-231 cells, with the ED50CI of 0.70 and 0.62, respectively. The Western blotting data showed that the combination of Cur and ADM could enhance the cleavage of PARP, and decrease the expression of Bcl-2, but had no affect on the expression of Bax in MCF-7 cells. In addition, we found that the combination treatment could inhibit the activation of NF-κB induced by ADM. Conclusions Cur sensitizes breast cancer to ADM in vitro most likely via inhibiting the activation of NF-κB signaling induced by ADM and subsequent increasing the apoptosis.
关键词
细胞凋亡 /
姜黄素 /
ADM /
NF-κB
Key words
apoptosis /
curcumin /
adriamycin /
NF-κB
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