Expression of multidrug resistance (MDR) & effect of MDR inhibitor activity in renal cell carcinoma

Abstract

[한글]

[영문]Purpose: Renal cell carcinoma (RCC) is instrisically resistant to chemotherapy, because 80-90% of RCC express multidrug resistance (MDR)1 as energy-dependent efflux pump. 1B3PY1 is newly synthesized MDR1 inhibitor designed based on other MDR1 modulator-verapamil. In this study, we investigated the expression of MDR1 in Caki-2 RCC cell line and human RCC cell that was obtained from the patients, then each combination effect of taxol,doxorubicin with 1B3PY1 in cultured Caki-2 cell and human RCC cell. Materials and methods: Caki-2 RCC cell line, and clinical samples were obtained from 8 males and 2 females with conventional clear cell RCC who had metastatic lesions at operation. After cell culute of specimens, Expression of MDR1 in Caki-2 cell and human RCC cell was estimated by RT-PCR. Cytotoxicity of 1B3PY1 was investigated, and then combination effect of taxol, doxorubicin with 1B3PY1 in Caki-2 cell and human RCC cell were evaluated.Results: MDR1 was expressed in Caki-2 cell and human RCC cell. The MDR1 in human RCC cell was significantly higher than that of Caki-2 cell. New MDR1 inhibitor, 1B3PY1 revealed no cytotoxicity in Caki-2 cell and human RCC cell. Compared with IC50 of taxol or doxorubicin only, there were also no significant combination effect with taxol or doxorubicin and 1B3PY1 in Caki-2 cell. In human RCC cell, there was also no significant combination effect with taxol and 1B3PY1, whereas IC50 in group of doxorubicin and 1B3PY1 was significantly decreased compared with that of doxorubicin only, maximum difference of which was upto 19 times. Conclusions: As a new MDR1 inhibitor, we suggest IB3PY1 would give a perspective in the treatment of metastatic RCC. Further study will be needed.