Abe T, Mori T, Wakabayashi Y, Nakagawa M, Cole S P, Koike K, Kuwano M, Hori S
Department of Neurosurgery, Oita Medical University, Japan.
J Neurooncol. 1998 Oct;40(1):11-8. doi: 10.1023/a:1005954406809.
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.
两种不同的ATP结合膜糖蛋白，即170 kDa的P-糖蛋白（P-gp）和190 kDa的多药耐药蛋白（MRP），参与癌细胞多药耐药表型的形成。在用抗癌药物治疗时，P-gp的过表达在各种人类肿瘤中经常被观察到。在本研究中，我们探讨了癌症化疗后人类胶质瘤中MRP是否过表达。我们调查了胶质瘤患者肿瘤样本化疗前后MRP和P-gp的表达情况。在23例未治疗患者中有16例（70%）观察到MRP表达，在这16例MRP阳性患者中，MRP阳性细胞在全细胞群体中的比例为3%至32%。23例患者中有4例（18%）观察到P-gp阳性肿瘤，P-gp阳性细胞在全细胞群体中的比例为4%至23%。在所有接受检查的患者中，化疗后MRP阳性或P-gp阳性胶质瘤细胞的比例与化疗前相比有所增加。我们未观察到MRP或P-gp的表达与肿瘤分级之间存在统计学上的显著相关性。这些结果表明，MRP以及P-gp可能参与人类胶质瘤的获得性或固有耐药性。
