흰쥐에서 기원한 전립선 상피세포인 NRP-152에서 Tamsulosin에 의해 유도되는 세포고사와 Clusterin의 발현에 관한 연구

Purpose: The aim of this study was to know whether and how tamsulosin induces apoptosis of normal rat prostate cells, and the relationship between apoptosis and clusterin expression. Materials and Methods: We used a prostate cell line, NRP-152 cells which are the basal epithelium cell originated from rat prostate. The NRP-152 cells were treated with various concentrations (50, 100, 200, 400 uM) of tamsulosin for 24 h. To evaluate apoptosis, the cultured NRP-152 cells were stained with Heochst 33258 and Propidium Iodide (PI) without fixation. We also examined DNA fragmentation analysis to confirm apoptosis. In addition, to elucidate the signal transduction pathway by which apoptosis is induced, we examined Bcl-2 family proteins such as Bcl-2, Bax, Bad, Bcl-xL, and Bim by real-time RT-PCR. Results: After tamsulosin treatment, the rate of apoptosis was 25% at 100μM, 50% at 200μM, and 63% at 400μM, whereas the rate of necrosis was 10% at 100μM, 38% at 200μM, and 56% at 400μM. DNA fragmentation was also gradually increased and the highest at 400μM, similar to apoptotic cell rates. As a result of real-time RT-PCR, there was significant difference of Bcl-2 and Bim mRNA expression among the groups. Expression of clusterin protein was significantly increased after treatment of tamsulosin, even as low as 50μM concentration. Conclusion: These results demonstrate that tamsulosin causes the cell death of NRP-152 cells, displaying low concentration of tamsulosin induces apoptosis, but high concentration occurs necrosis. Bim, a proapoptotic factor of the Bcl-2 family, expression was increased in the cells treated with tamsulosin, whereas Bcl-2 expression was decreased. The present study suggests that clusterin may play a role in the process of apoptosis induced by tamsulosin and Bim could be involved in the apoptosis. (J. Korean Continence Society 2006;10:132-139) KCI Citation Count: 0