姜黄素通过诱导p21（WAF1/CIP1）和C/EBPβ表达并抑制NF-κB激活来增强化疗药物对前列腺癌细胞的细胞毒性。
Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation.
作者信息
Hour Tzyh-Chyuan, Chen Jun, Huang Chao-Yuan, Guan Jing-Yi, Lu Shiu-Hui, Pu Yeong-Shiau
机构信息
Department of Urology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan, Republic of China.
出版信息
Prostate. 2002 May 15;51(3):211-8. doi: 10.1002/pros.10089.
BACKGROUND
The modulatory effects and molecular mechanisms of curcumin (CCM) on the cytotoxicity of chemotherapeutic agents to prostate cancer cells were explored.
METHODS
The combined effects of CCM and chemotherapeutic agents were examined by three different administration schedules (one concurrent and two sequential treatments) in two androgen-independent prostate cancer (AIPC) cells (PC-3 and DU145). Alteration of cell cycle progression, protein levels, and transcriptional activation in PC-3 cells were assayed by flow cytometry, Western blotting, and gel shift assay, respectively.
RESULTS
The combined effects of CCM --> chemotherapeutic agent schedule showed the greatest synergistic cytotoxicity when compared to the other two schedules in both cells. CCM induced a significant G1 arrest in PC-3, which may be mediated by the induction of p21(WAF1/CIP1) and C/EBPbeta. Moreover, CCM was able to inhibit both the constitutional and TNF-alpha-induced NF-kappaB activation in a time-dependent manner.
CONCLUSIONS
The incorporation of CCM into cytotoxic therapies may be a promising strategy for the treatment of AIPC.
背景
探讨姜黄素（CCM）对化疗药物对前列腺癌细胞细胞毒性的调节作用及其分子机制。
方法
在两种雄激素非依赖性前列腺癌（AIPC）细胞（PC-3和DU145）中，通过三种不同的给药方案（一种同时给药和两种序贯治疗）检测CCM与化疗药物的联合作用。分别通过流式细胞术、蛋白质印迹法和凝胶迁移试验检测PC-3细胞中细胞周期进程、蛋白质水平和转录激活的变化。
结果
与其他两种给药方案相比，CCM→化疗药物给药方案在两种细胞中均显示出最大的协同细胞毒性。CCM诱导PC-3细胞显著的G1期阻滞，这可能由p21（WAF1/CIP1）和C/EBPβ的诱导介导。此外，CCM能够以时间依赖性方式抑制组成型和TNF-α诱导的NF-κB激活。
结论
将CCM纳入细胞毒性治疗可能是治疗AIPC的一种有前景的策略。
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