Inhibition of proliferation of prostate cancer cell line, PC-3, in vitro and in vivo using (-)-gossypol
Inhibition of proliferation of prostate cancer cell line, PC-3, in vitro and in vivo using (-)-gossypol
复制标题
使用 (-)-棉酚在体外和体内抑制前列腺癌细胞系 PC-3 的增殖
DOI：
10.1038/aja.2009.87
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发表时间：
2010-05-01
影响因子：
2.9
通讯作者：
Wu, Dao-Cheng
中科院分区：
文献类型：
--
作者：
Zhang, Xian-Qing;Huang, Xiao-Feng;Wu, Dao-Cheng
我们研究了（-）-棉酚在体外和体内对人前列腺癌细胞系PC 3的抗增殖活性，以阐明其潜在的分子机制。采用MTT法检测细胞生长情况，流式细胞仪、TUNEL法和电镜观察细胞凋亡情况。免疫组化法检测肿瘤组织中增殖细胞核抗原（PCNA）、Bcl-2、CD 31、caspase-3和caspase-8的表达。产生50%细胞抑制的药物浓度（IC 50值）为4.74 μ g mL（-1）。在PC-3肿瘤异种移植研究中，（-）-棉酚（> 5 mg kg（-1））每天给药一次，持续7天，以剂量依赖性方式显著抑制肿瘤生长。免疫组化结果显示，（-）-棉酚可增强肿瘤组织中caspase-3和caspase-8的表达，降低PCNA、Bcl-2和CD 31的表达。结果表明，（-）-棉酚的抗肿瘤作用可能与细胞凋亡和抑制血管生成有关。
We investigated the antiproliferative activity of (-)-gossypol on the human prostate cancer cell line PC3 in vitro and in vivo to elucidate its potential molecular mechanisms. Cell growth and viability were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and electron microscopy. Expression of proliferating cell nuclear antigen (PCNA), Bcl-2, CD31, caspase-3 and caspase-8 in tumour tissue was determined by immunohistochemistry. The drug concentration that yielded 50% cell inhibition (IC50 value) was 4.74 mu g mL(-1). In the PC-3 tumour xenograft study, (-)-gossypol (> 5 mg kg(-1)) given once a day for 7 days significantly inhibited tumour growth in a dose-dependent manner. Immunohistochemical analysis revealed that (-)-gossypol enhanced caspase-3 and caspase-8 expression and decreased the expression of PCNA, Bcl-2 and CD31 in tumour tissues. It suggested that cell apoptosis and inhibition of angiogenesis might contribute to the anticancer action of (-)-gossypol.