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苦参碱抑制雄激素非依赖性前列腺癌细胞系 PC-3 的增殖并诱导其凋亡。

Matrine inhibits proliferation and induces apoptosis of the androgen‑independent prostate cancer cell line PC-3.

机构信息

Department of Urology, The Second Affiliated Hospital of Medical College of Xi'an, JiaoTong University, Xi'an, Shaanxi 710004, PR China.

出版信息

Mol Med Rep. 2012 Mar;5(3):783-7. doi: 10.3892/mmr.2011.701. Epub 2011 Dec 9.

Abstract

Current strategies to treat androgen-independent prostate cancer are associated with a number of challenges and are not yet curative. Matrine is a naturally occurring alkaloid extracted from the Chinese herb Sophora flavescens. Matrine has shown anti-proliferative properties in a number of types of cancer, including breast, gastric, lung and pancreatic tumors. Matrine was also found to promote apoptosis and inhibit invasion of cancer cells. We evaluated the antitumor effects of matrine on androgen-independent PC-3 prostate cancer cells. The effects of matrine on cell cycle progression and apoptosis of PC-3 cells were tested. Matrine-treated PC-3 cells underwent G0/G1 cell cycle arrest. There was a significant reduction in the number of S phase and G2/M phase cells in the treated group when compared to untreated cells. Flow cytometry, as well as Annexin-V/PI staining, showed a significant, dose-dependent increase in the number of early, as well as late, stage apoptotic cells in matrine-treated cells compared to untreated cells. There was also an increase in the number of necrotic cells in the matrine-treated group when compared to untreated cells. Matrine treatment resulted in increased levels of caspase-3 and Bax and decreased levels of Bcl-2. Our data suggest that matrine inhibits the proliferation of androgen-independent prostate cancer cells by causing G0/G1 cell cycle arrest and promoting apoptosis. Matrine‑induced apoptosis was mediated by downregulation of Bcl-2/Bax ratios and upregulation of caspase-3 levels. Based on our data, we suggest that matrine may be a novel addition to the current arsenal of strategies used to treat androgen-independent prostate cancer.

摘要

目前治疗雄激素非依赖性前列腺癌的策略存在诸多挑战,且尚未能根治。苦参碱是从中国草药苦参中提取的一种天然生物碱。苦参碱在多种类型的癌症中显示出抗增殖特性,包括乳腺癌、胃癌、肺癌和胰腺癌。苦参碱还被发现能促进癌细胞凋亡和抑制侵袭。我们评估了苦参碱对雄激素非依赖性 PC-3 前列腺癌细胞的抗肿瘤作用。检测了苦参碱对 PC-3 细胞细胞周期进展和凋亡的影响。苦参碱处理的 PC-3 细胞经历 G0/G1 细胞周期停滞。与未处理的细胞相比,处理组 S 期和 G2/M 期细胞的数量明显减少。流式细胞术以及 Annexin-V/PI 染色显示,与未处理的细胞相比,苦参碱处理的细胞中早期和晚期凋亡细胞的数量显著增加,呈剂量依赖性。与未处理的细胞相比,苦参碱处理组的坏死细胞数量也增加。苦参碱处理导致 caspase-3 和 Bax 水平升高,Bcl-2 水平降低。我们的数据表明,苦参碱通过引起 G0/G1 细胞周期停滞和促进细胞凋亡来抑制雄激素非依赖性前列腺癌细胞的增殖。苦参碱诱导的凋亡是通过下调 Bcl-2/Bax 比值和上调 caspase-3 水平介导的。基于我们的数据,我们认为苦参碱可能是治疗雄激素非依赖性前列腺癌的现有策略的一种新的补充。

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