Herceptin联合9-顺式视黄酸对ErbB2阳性乳腺癌细胞的抑制作用及其相关分子机制的研究  

Synergistic inhibitory effects of Herceptin and 9-cis retinoic acid on 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：《免疫学杂志》2007年第6期627-630,635,共5页Immunological Journal

基　　金：国家自然科学基金资助项目(30300285)

摘　　要：目的探讨Herceptin联合9-顺式视黄酸对ErbB2阳性乳腺癌细胞的协同增殖抑制效应及其分子机制。方法利用MTT法检测经Herceptin、9-顺式视黄酸单独和联合作用后HER2/neu阳性的MDA-MB-453乳腺癌细胞的增殖活性的变化,在此基础上,利用免疫印记和半定量PCR法对HER2/neu、RXR以及COX-2的表达进行检测,同时利用ELISA法检测细胞培养上清内PGE-2的水平变化。结果一定剂量的Herceptin和9-顺式视黄酸能够有效协同抑制MDA-MB-453细胞的增殖活性。经二者联合作用后,磷酸化、非磷酸化的ErbB2以及COX-2的表达较对照组均显著下降,而RXRα的表达则无明显变化。同时,二者联合作用还能有效降低细胞PGE-2的分泌水平。结论Herceptin和9-顺式视黄酸可在体外分别通过抑制HER2/neu和COX-2的表达和活性来达到协同抑制HER2/neu阳性乳腺癌的作用。Objective To explore the synergistic effects of Herceptin and 9-cis retinoic acid （RA） on HER2/neu-positive breast cancer cells and the associated molecular mechanism. Methods The inhibitory effects of Herceptin and 9-cis RA on the proliferation of MDA-MB-453 cells were detected by the MrIT assay. And then, the mRNA and protein expressions of ErbB2, pErbB2, RXRa, and COX-2 were analyzed by RT-PCR and Western blotting. At the same time, the excretion of PGE-2 was tested by ELISA assay. Results Herceptin and 9-cis RA synergistically inhibited the proliferation of MDA-MB-453 cells in vitro. The expressions of ErbB2, pErbB2, and COX-2 were notably down-regulated, while the RXRα expression exhibited no remarkable change. Also, the excretion of PGE-2 was significantly inhibited by the co-treatment. Conclusion Herceptin and 9-cis RA could exert synergistic inhibitory effects on ErbB2-positive breast cancer cells by influencing the expression and activity of ErbB2 and COX-2 as well as the PGE-2 synthesis.

关 键 词：HERCEPTIN 9-顺式视黄酸 ERBB2 环氧化酶-2 前列腺素E-2 MDA—MB-453细胞 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]