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P13K／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、P13K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P13K／Akt信号途径有关。

Relationship between PI3K/Akt pathway and genistein sensitizing hi 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.