Expression of multidrug resistance protein gene in patients with glioma after chemotherapy

Abstract

Two different ATP-binding membrane glycoproteins, the 170 kDa P-glycoprotein (P-gp) and the 190 kDa multidrug resistance protein (MRP), are involved in the acquisition of multidrug resistance phenotypes in cancer cells. Overexpression of P-gp is often observed in various human tumors when treated with anticancer agents. In this study, we asked whether MRP was overexpressed in human gliomas after cancer chemotherapy. We investigated expression of MRP and P-gp before and after chemotherapy in tumor samples from patients with glioma. MRP expression was observed in 16 (70%) of 23 untreated patients, and the proportion of MRP-positive cells in the whole cell population ranged from 3 to 32% in the 16 MRP-positive patients. P-gp-positive tumors were observed in 4 (18%) of 23 patients, and the proportional rates of P-gp-positive cells in the whole cell population ranged from 4 to 23%. The proportional rate of MRP-positive or P-gp-positive glioma cells increased after chemotherapy when compared with that before chemotherapy in all patients examined. We could observe no statistically significant correlation between expression of MRP or P-gp and tumor grade. These results suggest that MRP as well as P-gp may be involved in acquired or intrinsic drug resistance in human glioma.