柠檬酸锌复合物对激素难治性前列腺癌的抗增殖作用。
Antiproliferative effects of zinc-citrate compound on hormone refractory prostate cancer.
机构信息
Department of Urology, College of Medicine, the Catholic University of Korea, Seoul 137701, Korea.
出版信息
Chin J Cancer Res. 2012 Jun;24(2):124-9. doi: 10.1007/s11670-012-0124-9.
OBJECTIVE
To investigate the antiproliferative effects of zinc-citrate compound on hormone refractory prostate cancer (HRPC).
METHODS
HRPC cell line (DU145) and normal prostate cell line (RWPE-1) were treated with zinc, citrate and zinc-citrate compound at different time intervals and concentrations to investigate the effect of zinc-citrate compound. Mitochondrial (m)-aconitase activity was determined using aconitase assay. DNA laddering analysis was performed to investigate apoptosis of DU145 cells. Molecular mechanism of apoptosis was investigated by Western blot analysis of P53, P21(waf1), Bcl-2, Bcl-xL and Bax, and also caspase-3 activity analysis.
RESULTS
Treatment with zinc-citrate compound resulted in a time- and dose-dependent decrease in cell number of DU145 cells in comparison with RWPE-1. M-aconitase activity was significantly decreased. DNA laddering analysis indicated apoptosis of DU145 cells. Zinc-citrate compound increased the expression of P21(waf1) and P53, and reduced the expression of Bcl-2 and Bcl-xL proteins but induced the expression of Bax protein. Zinc-citrate compound induced apoptosis of DU145 cells by activation of the caspase-3 pathway.
CONCLUSION
Zinc-citrate compound can induce apoptotic cell death in DU145, by caspase-3 activation through up-regulation of apoptotic proteins and down-regulation of antiapoptotic proteins.
目的
研究柠檬酸锌复合物对激素难治性前列腺癌（HRPC）的抗增殖作用。
方法
用不同时间间隔和浓度的锌、柠檬酸和柠檬酸锌复合物处理 HRPC 细胞系（DU145）和正常前列腺细胞系（RWPE-1），以研究柠檬酸锌复合物的作用。用顺乌头酸酶测定法测定线粒体（m）-顺乌头酸酶活性。通过 DNA 梯状带分析研究 DU145 细胞的凋亡。通过 Western blot 分析 P53、P21（waf1）、Bcl-2、Bcl-xL 和 Bax，以及 caspase-3 活性分析，研究凋亡的分子机制。
结果
与 RWPE-1 相比，柠檬酸锌复合物处理导致 DU145 细胞数量随时间和剂量呈依赖性减少。m-顺乌头酸酶活性显著降低。DNA 梯状带分析表明 DU145 细胞发生凋亡。柠檬酸锌复合物增加了 P21（waf1）和 P53 的表达，降低了 Bcl-2 和 Bcl-xL 蛋白的表达，但诱导了 Bax 蛋白的表达。柠檬酸锌复合物通过激活 caspase-3 途径诱导 DU145 细胞凋亡。
结论
柠檬酸锌复合物可通过上调促凋亡蛋白和下调抗凋亡蛋白，通过 caspase-3 激活诱导 DU145 细胞发生凋亡性细胞死亡。
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