PI3K/Akt与染料木黄酮增敏阿霉素体外化疗人乳腺癌 MDA-MB-453 细胞的关系研究

目的 观察染料木黄酮(GEN)对HER2/neu高表达人乳腺癌MDA-MB-453细胞PI3K/Akt信号途径的抑制作用,探讨其在GEN增敏阿霉素(DOX)体外化疗乳腺癌MDA-MB-453细胞中的作用.方法 GEN、PI3K特异性抑制剂渥曼青霉素(WT)和DOX单独或联合处理体外培养的MDA-MB-453细胞,免疫细胞化学法检测HER-2/neu蛋白表达,免疫印迹法检测总Akt和磷酸化Akt蛋白(p-Akt)表达.结果 GEN对MDA-MB-453细胞HER2/neu和总Akt蛋白没有明显影响,但可明显降低p-Akt蛋白水平;同时WT也能明显降低p-Akt蛋白,并显著增强DOX抑制MDA-MB-453细胞生长的作用.结论 GEN增敏DOX体外化疗乳腺癌MDA-MB-453细胞株可能与其抑制PI3K/Akt信号途径有关.

Relationship between PI3K/Akt pathway and genistein sensitizing human breast cancer MDA-MB-453 cell line to doxorubicin in vitro

Objective To investigate the inhibitory effect of genistein on PI3K/Akt signal pathway in HER2/neu-overexpressing breast cancer MDA-MB-453 cells and the role of PI3K/Akt signal pathway in genistein sensitizing MDA-MB-453 cells to chemotherapeutic agent doxorubicin in vitro. Methods MDA-MB-453 breast cancer cells were treated with genistein or wortmannin or doxorubicin or genistein doxorubicin or wortmannin doxorubicin in vitro. The expressions of HER2/neu protein and Akt and p-Akt protein in MDA-MB-453 cells were observed by immunocytochemistry and Western blotting, respectively. Results Genistein did not change the expression of HER2/neu or total Akt protein in MDA-MB-453 cells, but significantly decreased phosphorylated Akt (p-Akt) level. Wortmannin also obviously decreased the p-Akt protein in MDA-MB-453 cells and sensitized the cells to the chemotherapeutic agent doxorubicin. Conclusion Genistein sensitizing MDA-MB-453 cells to doxorubicin in vitro may be correlated with the inhibition of PI3K/Akt signal pathway.