Furuya Y, Akimoto S, Yasuda K, Ito H
Department of Urology, School of Medicine, Chiba University, Japan.
Anticancer Res. 1997 Nov-Dec;17(6D):4589-93.
Androgen-dependent prostate cancer cells eventually progress to androgen -independent cells after hormonal manipulation. Due to chemotherapeutic drug resistance and toxic side effects, new targets for antineoplastic therapy are urgently needed. In the present study, cerulenin, a fatty acid synthase inhibitor, was used to induce the death of androgen-independent prostate cancer cells. Cerulenin induces the apoptosis of TSU-prl cells based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability. During apoptotic process induced by the agents, expression of cyclin-dependent kinase inhibitors p21 and p27 increased, whereas expression of cyclin D1 decreased. Flow cytometric analysis showed that the treatment resulted in a block in G2/M of the cell cycle. These results demonstrated that inhibition of fatty acid synthesis could be a target to treat hormone-independent prostate cancer cells via apoptosis, and cyclin-dependent kinase inhibitors played some role during apoptotic pathway.
雄激素依赖性前列腺癌细胞在激素治疗后最终会发展为雄激素非依赖性细胞。由于化疗药物耐药性和毒副作用，迫切需要抗肿瘤治疗的新靶点。在本研究中，脂肪酸合酶抑制剂浅蓝菌素被用于诱导雄激素非依赖性前列腺癌细胞死亡。浅蓝菌素根据DNA片段化的时间顺序、形态学变化和细胞活力丧失诱导TSU-prl细胞凋亡。在这些药物诱导的凋亡过程中，细胞周期蛋白依赖性激酶抑制剂p21和p27的表达增加，而细胞周期蛋白D1的表达降低。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，抑制脂肪酸合成可能是通过凋亡治疗激素非依赖性前列腺癌细胞的一个靶点，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。
