染料木黄酮影响MDA-MB-453细胞对紫杉醇化疗敏感性的机制  

STUDY ON THE MECHANISMS OF GENISTEIN AFFECTING THE CHEMOSENSITIVITY OF HUMAN BREAST CANCER CELL LINE MDA-MB-453 TO PACLITAXEL IN VITRO

作　　者：张红[1] 朱俊东[2] 糜漫天[2] 郎海滨[2] 

机构地区：[1]中国航天员科研训练中心,北京100094 [2]第三军医大学军事预防医学院营养与食品卫生学教研室,重庆400038

出　　处：《营养学报》2007年第5期494-497,共4页Acta Nutrimenta Sinica

摘　　要：目的:探讨染料木黄酮(genistein,GEN)影响紫杉醇(paclitaxel,PTX)体外化疗HER2/neu高表达人乳腺癌细胞株MDA-MB-453敏感性的作用机制。方法:GEN和PTX单独或联合处理MDA-MB–453细胞,流式细胞仪检测细胞周期分布,免疫细胞化学法检测HER2/neu蛋白、Westernblot检测Akt、p-Akt、CyclinB1、CDK1蛋白表达的变化。结果:GEN和PTX单独作用时MDA-MB-453细胞分别阻滞于G1/S期和G2/M期,HER2/neu、总Akt和CDK1蛋白水平均没有明显变化,但GEN可显著降低p-Akt和CyclinB1蛋白水平,而PTX则明显增加CyclinB1蛋白水平,二者联合处理时GEN拮抗PTX增加CyclinB1蛋白水平和诱导G2/M期阻滞的作用。结论:GEN拮抗PTX增加cyclin B1蛋白水平和G2/M期阻滞的作用,可能是其降低PTX体外化疗MDA-MB-453细胞敏感性的机制之一。Objective： To investigate the mechanisms of genistein （GEN） affecting the chemosensitivity of human breast cancer cell line MDA-MB-453 to paclitaxel （PTX） in vitro. Method： HER2/neuoverexpressing breast cancer cells MDA-MB-453 were treated by GEN, PTX alone or combined in vitro. Cell cycle was measured by flow cytometry. The expression of HER2/neu protein was observed by immunocytochemistry and. Akt, p-AM, cyclin B1 and CDK1 protein by Western blot. Results： Cell cycle of MDA-MB-453 cells was blocked at G1/S after treatment of GEN, while at G2/M after treatment with PTX alone. Both GEN and PTX did not change the expression of HER2/neu, total Akt and CDK1 in MDA-MB-453 cells, but GEN significantly decreased p-Akt and cyclin B1 level, and PTX obviously increased cyclinB 1 level. GEN antagonized the effects of PTX on level of cyclin B 1 protein and blockage of G2/M in MDA-MB-453 cells after treatment with GEN and PTX in combination. Conclusion： The antagonism effects of GEN on the increase of cyclin B 1 and blockage of G2/M induced by PTX may be one of the mechanisms of GEN affecting the chemosensitivity of MDA-MB-453 cells to PYX.

关 键 词：GEN 紫杉醇 人乳腺癌细胞MDA-MB-453 CYCLINB1 P-AKT CDK1 

分 类 号：R737.9[医药卫生—肿瘤]