Furuya Y, Ohta S, Ito H
Department of Urology, School of Medicine, Chiba University, Japan.
Anticancer Res. 1997 May-Jun;17(3C):2089-93.
New treatments for hormone-independent tumor are urgently needed since androgen-dependent cancer cells eventually progress to -independent cells after hormonal manipulation. In the present study, etoposide and camptothecin were used to induce proliferation-dependent death of these cells. Each of the agents, at the doses used, induces the apoptosis of AT-3, CS 2, and TSU-pr1 cells based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability. Northern blot analysis was used to identify a series of genes whose expression is enhanced during the apoptotic pathway. During the apoptotic process induced by the agents, expression of cyclin-dependent kinase inhibitor p27 increased. Flow cytometric analysis showed that the treatment resulted in a block in G2/M of the cell cycle. These results demonstrate that these cells retain the ability to undergo apoptosis by etoposide and camptothecin, and cyclin-dependent kinase inhibitor plays some role during apoptotic pathway.
由于雄激素依赖的癌细胞在激素处理后最终会发展为激素非依赖型细胞，因此迫切需要针对激素非依赖型肿瘤的新治疗方法。在本研究中，依托泊苷和喜树碱被用于诱导这些细胞发生增殖依赖性死亡。在所使用的剂量下，每种药物都基于DNA片段化的时间顺序、形态学变化和细胞活力丧失诱导AT-3、CS 2和TSU-pr1细胞凋亡。采用Northern印迹分析来鉴定一系列在凋亡途径中表达增强的基因。在药物诱导的凋亡过程中，细胞周期蛋白依赖性激酶抑制剂p27的表达增加。流式细胞术分析表明，该处理导致细胞周期在G2/M期阻滞。这些结果表明，这些细胞保留了被依托泊苷和喜树碱诱导凋亡的能力，并且细胞周期蛋白依赖性激酶抑制剂在凋亡途径中发挥了一定作用。
