Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, 110004, Shenyang, People's Republic of China.
Med Oncol. 2010 Sep;27(3):960-7. doi: 10.1007/s12032-009-9317-6. Epub 2009 Sep 23.
The effects of Lewis Y antigen on the gene expression of multiple drug resistance-associated proteins in human ovarian cancer RMG-I-H cells were unclear by now. In this study, we detected the gene expression of multiple drug resistance-associated proteins (MRP) in RMG-I-H cells and RMG-I-H cells treated with anti-Lewis Y monoclonal antibody to investigate the association between Lewis Y antigen and the gene expression of drug resistance-associated proteins. Compared with RMG-I cells, the expression of MRP1, MRP2, protein kinase C-alpha (PKC-alpha), and topoisomerase I (Topo I) mRNAs in RMG-I-H cells were significantly upregulated, while the MDR-1 mRNA was downregulated. Immunochemistry analyses indicated that the in vitro and in vivo expression levels of MDR-1 protein (P-gp) in RMG-I-H cells were significantly higher than those in RMG-I cells. After RMG-I-H cells were treated with anti-Lewis Y monoclonal antibody, the expression levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs gradually decreased with the prolongation of treatment duration. In contrast, no obvious changes were noted in the expression levels of these mRNAs in the non-treatment group. At 6 h after treatment, the relative levels of MDR-1, MRP1, MRP2, PKC-alpha, and Topo I mRNAs in the antibody treatment group were significantly lower than those in the non-treatment group. In conclusion, Lewis Y antigen is closely associated with regulating the gene expression of multiple drug resistance-associated proteins.
目前尚不清楚 Lewis Y 抗原对人卵巢癌细胞 RMG-I-H 中多种耐药相关蛋白基因表达的影响。在本研究中,我们检测了 RMG-I-H 细胞和用抗 Lewis Y 单克隆抗体处理的 RMG-I-H 细胞中多种耐药相关蛋白(MRP)的基因表达,以探讨 Lewis Y 抗原与耐药相关蛋白基因表达之间的关系。与 RMG-I 细胞相比,RMG-I-H 细胞中 MRP1、MRP2、蛋白激酶 C-α(PKC-α)和拓扑异构酶 I(Topo I)mRNA 的表达明显上调,而 MDR-1 mRNA 的表达下调。免疫化学分析表明,RMG-I-H 细胞中 MDR-1 蛋白(P-gp)的体外和体内表达水平明显高于 RMG-I 细胞。用抗 Lewis Y 单克隆抗体处理 RMG-I-H 细胞后,随着处理时间的延长,MDR-1、MRP1、MRP2、PKC-α和 Topo I mRNA 的表达水平逐渐降低。相比之下,未处理组这些 mRNA 的表达水平没有明显变化。处理 6 小时后,抗体处理组 MDR-1、MRP1、MRP2、PKC-α和 Topo I mRNA 的相对水平明显低于未处理组。总之,Lewis Y 抗原与调节多种耐药相关蛋白基因表达密切相关。