Chekhun V F, Lukyanova N Yu, Urchenko O V, Kulik G I
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine, Kyiv 03022, Ukraine.
Exp Oncol. 2005 Sep;27(3):191-5.
To study the expression of proteins that characterize drug resistance, proliferation and apoptosis of human ovarian carcinoma cells.
The study was carried out on human ovarian carcinoma A2780 cells and on the A2780/DDP8 subline resistant to cisplatin. Expression of the surface and intracellular antigens (p53, Bcl-2, CD95, antigen of proliferating cells, metallothioneins, drug resistance proteins (P-glycoprotein (P-gp), glutathione-S-transferase), molecules of adhesion (E-cadherin, alpha- and beta-catenins) was studied by immunocytochemical method.
It has been shown that the formation of the resistance to cisplatin in A2780/DDP8 cells is accompanied by the increase of expression of glutathione-S-transferase and Bcl-2, by the decrease of expression of CD95-antigene and proliferation potential of the cells, by appearance of EGF receptors and elevation of expression level of E-cadherin, alpha- and beta-catenins, proving the enhancement of adhesive properties of tumor cells.
Antiapoptotic program seems to be the leading mechanism of the development of the resistance to cisplatin in A2780/DDP8 cells and is realized via high expression of Bcl-2. During the development of drug resistance of A2780/DDP cells, the program of glutathione detoxification is functionally replacing the decrease of the content of metallothioneins.
研究表征人卵巢癌细胞耐药性、增殖和凋亡的蛋白质表达情况。
对人卵巢癌A2780细胞和顺铂耐药的A2780/DDP8亚系细胞进行研究。采用免疫细胞化学方法研究表面和细胞内抗原（p53、Bcl-2、CD95、增殖细胞抗原、金属硫蛋白、耐药蛋白（P-糖蛋白（P-gp）、谷胱甘肽-S-转移酶））、黏附分子（E-钙黏蛋白、α-连环蛋白和β-连环蛋白）的表达。
结果表明，A2780/DDP8细胞对顺铂耐药性的形成伴随着谷胱甘肽-S-转移酶和Bcl-2表达的增加、CD95抗原表达和细胞增殖潜能的降低、表皮生长因子受体的出现以及E-钙黏蛋白、α-连环蛋白和β-连环蛋白表达水平的升高，这证明肿瘤细胞黏附特性增强。
抗凋亡程序似乎是A2780/DDP8细胞对顺铂耐药性产生的主要机制，并且通过Bcl-2的高表达得以实现。在A2780/DDP细胞耐药性形成过程中，谷胱甘肽解毒程序在功能上替代了金属硫蛋白含量的降低。
