Change of MDR Gene Expression and Glutathione Metabolism during Long Standing Low-dose Cisplatin Exposure in Bladder Carcinoma Cell Line

Lee, Eun Sik; Kim, Soo Woong; Yoon, Sang Jin; Lee, Hae Won; Ahn, Han Jong; Lee, Chong Wook

Abstract

Resistance to anticancer chemotherapeutic drugs remains a major obstacle in cancer chemotherapy. A variety of mechanisms responsible for drug resistance has been posed. Mdr gene overexpression and detoxification by glutathione are believed to be involved in such mechanisms. Recently, we established two low-dose cisplatin-resistant human bladder cancer cell lines, T24RO.5 and T24R1, which showed resistance at O.5 hg/ml and 1 hg/ml of cisplatin, respectively. The resistance of T24RO.5 and T24R1 cells to cisplatin were 9.4 and 9.37 fold compared to that of the parental T24 cells In this study, we investigated the total glutathione content and p-glycoprotein expression, a mdr gene product, in parent and resistant cell lines to elucidate the drug resistance mechanism to cisplatin. Glutathione content was measured by biochemical method. P-glycoprotein expression was measured by flowcytometry using monoclonal antibody to p-glycoprotein. Glutathione content and p-glycoprotein expression were not different between parental and all resistant cell lines. These results suggest that mdr gene and glutathione do not play a role in cisplatin resistance mechanism in these low-dose cisplatin-resistant cell lines. Further work will be necessary to determine the mechanism of drug resistance in this model.