Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action
Suppression of growth of highly-metastatic human breast cancer cells by norcantharidin and its mechanisms of action
复制标题
DOI：
10.1007/s10616-009-9221-0
复制
发表时间：
2009-07
期刊：
影响因子：
2.2
通讯作者：
Yan Huang;Qian Liu;Kun Liu;K. Yagasaki;Guoyin Zhang
中科院分区：
文献类型：
--
作者：
Yan Huang;Qian Liu;Kun Liu;K. Yagasaki;Guoyin Zhang
通过体外和离体试验研究了去甲斑蝥素 (NCTD) 对高转移性人乳腺癌细胞生长的影响。结果表明，去甲斑蝥素以6、30和60μmol/L浓度去甲斑蝥素处理24、48和72小时后，以剂量和时间依赖性方式抑制人乳腺癌MDA-MB-231细胞系的体外生长。此外，在 15 分钟和 30 分钟静脉注射 NCTD 后，经 NCTD 处理的兔子的血清显着抑制了离体癌细胞的生长。 Hoechst 33258染色和流式细胞术分析表明，NCTD处理细胞48小时后，MDA-MB-231细胞出现典型的凋亡形态学变化，细胞周期停滞在G2/M期。此外，NCTD下调抗凋亡蛋白Bcl-2的表达，上调促凋亡蛋白Bax的表达，最终导致MDA-MB-231细胞中Bcl-2/Bax比值降低。此外，浓度为 6、30 和 60 μmol/L 的 NCTD 剂量依赖性地降低了乳腺癌细胞系中 Akt 的磷酸化和 NF-κB 的表达。 NCTD诱导细胞凋亡和细胞周期停滞以及降低Bcl-2/Bax比值可能是NCTD抑制MDA-MB-231细胞生长的重要作用机制，这与抑制Akt和NF-κB信号传导有关。我们的研究结果表明，去甲斑蝥素在人类乳腺癌的治疗中可能具有广泛的治疗和/或辅助治疗应用。
The effects of norcantharidin (NCTD) on the growth of highly-metastatic human breast cancer cells were investigated by in vitro and ex vivo assays. Our results indicated that norcantharidin inhibited the in vitro growth of human breast cancer MDA-MB-231 cell line in dose- and time-dependent manners after the cancer cells were treated with norcantharidin at the concentrations of 6, 30 and 60 μmol/L for 24, 48 and 72 h. Moreover, the sera from the NCTD-treated rabbits after intravenous injection of NCTD at 15 and 30 min significantly suppressed the growth of the cancer cells ex vivo. The analyses by Hoechst 33258 staining and flow cytometry showed that the typical apoptotic morphological changes appeared and cell cycles arrested at G2/M phase in MDA-MB-231 cells after the cells were treated for 48 h with NCTD. In addition, NCTD down-regulated the expressions of anti-apoptotic protein Bcl-2 and up-regulated the expressions of pro-apoptotic protein Bax, eventually leading to the reduction of Bcl-2/Bax ratio in MDA-MB-231 cells. Furthermore, NCTD at concentrations of 6, 30 and 60 μmol/L dose-dependently reduced the phosphorylation of Akt and NF-κB expression in the breast cancer cell line. Induction of apoptosis and cell cycle arrest as well as reduction of Bcl-2/Bax ratio by NCTD may be the important mechanisms of action of NCTD suppressing the growth of MDA-MB-231 cells, which are associated with inhibition of the Akt and NF-κB signaling. Our findings suggest that norcantharidin may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer.