赫赛汀及9-顺式视黄酸对乳腺癌联合抑制作用  

Inhibitory effects of herceptin and 9-cis retinoic acid on cell cycle progression of HER2/neu-positive breast cancer cells and associated molecular mechanism

作　　者：郎海滨[1] 糜漫天[1] 朱俊东[1] 

机构地区：[1]第三军医大学营养与食品卫生学教研室重庆市营养与食品安全重点实验室,重庆400038

出　　处：《中国公共卫生》2008年第3期311-312,共2页Chinese Journal of Public Health

基　　金：国家自然科学基金(30300285)

摘　　要：目的探讨赫赛汀联合9-顺式视黄酸对ErbB2阳性乳腺癌细胞周期进程及分布的影响及其相应的分子机制。方法利用流式细胞仪检测经赫赛汀、9-顺式视黄酸单独和联合作用后,癌基因(ErbB2/neu)阳性的MDA-MB-453乳腺癌细胞周期进程和分布的变化。在此基础上,利用免疫印记和半定量PCR法对CDK2、CyclinE、P27的表达进行检测,同时利用免疫沉淀法检测CyclinE/CDK2结合力的变化。结果与对照组比较,一定剂量的赫赛汀和9-顺式视黄酸可将MDA-MB-453细胞的周期进程阻遏于G0/G1期从而抑制其增殖活性。经2者联合作用后,CyclinE、CDK2的表达较对照组均有所下降,其中以CDK2的变化最为明显,而P27蛋白表达则明显升高。同时,2者联合作用还能有效降低CyclinE/CDK2的结合能力。结论赫赛汀和9-顺式视黄酸可在体外分别通过改变CyclinE、CDK2和P27的表达和活性起到协同抑制HrbB2/neu阳性乳腺癌的目的。Objective To explore the synergistic effects of herceptin and 9-cis RA on the cell cycle progression of HER2/neu-positive breast cancer cells and associated molecular mechanism.Methods After the treatment of MDA-MB-453 cells with herceptin and 9-cis RA,flow cytometry assay was employed to detect the inhibitory effects on cell cycle progression.After that,mRNA and protein expression of cyclin E,CDK2,and P27 were analyzed by RT-PCR and Western blotting.At the same time,the bingding affinity of cyclin E and CDK2 was tested by immunoprecepitation assay.Results Herceptin and 9-cis RA synergistically blocked the cell cycle progression of MDA-MB-453 cells in G0/G1 phase in vitro.The expression of cyclin E and CDK2 were notably down-regulated as well as the cyclin E/CDK2 binding affinity,while the P27 protein expression was remarkably up-regulated by the co-treatment.Conclusion Herceptin and 9-cis RA could exert synergistic inhibitory effects on cell cycle progression of ErbB2-positive breast cancer cells by influencing the expression and activity of cyclin E,CDK2 and P27.

关 键 词：赫赛汀 9-顺式视黄酸 ERBB2 细胞周期 MDA-MB-453细胞 乳腺癌 

分 类 号：R392.12[医药卫生—免疫学]