Genistein-Selenium Combination Induces Growth Arrest in Prostate Cancer Cells
Genistein-Selenium Combination Induces Growth Arrest in Prostate Cancer Cells
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DOI：
10.1089/jmf.2009.0199
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发表时间：
2010-08-01
影响因子：
2.4
通讯作者：
Johnson, Michelle
中科院分区：
文献类型：
--
作者：
Kumi-Diaka, James;Merchant, Kendra;Johnson, Michelle
转移性前列腺癌患者的预后仍然很差，尽管采取了传统的积极治疗方法。几项体外研究以及动物模型和流行病学研究表明，植物化学物质可以抗肿瘤，并可能对人类癌症具有保护作用。然而，作为一种被广泛研究的营养植物化学物质，金雀异黄素的潜在抗肿瘤作用一直是模棱两可的。本研究探讨了金雀异黄素-硒(Gn-Se)联合应用对PC3(激素非依赖性)和LNCaP(激素依赖性)前列腺癌细胞化疗敏感性和基质金属蛋白酶-2(MMP2)表达水平的影响。3-(4，5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium染色和三磷酸腺苷生物测定结果显示，金雀异黄素、硒和Gn-Se联合作用明显抑制LNCaP和PC3细胞的生长，且呈剂量和时间依赖性，且与激素状态无关，LNCaP和PC3对化疗药物的敏感性无明显差异。GN-Se联合用药对两种细胞的生长抑制作用最强。抑制生长是通过诱导细胞凋亡来实现的。治疗诱导的细胞凋亡级联是caspase依赖的，有证据表明存在另一条非caspase途径(S)。治疗还可诱导PC3和LNCaP细胞的基质金属蛋白酶-2表达水平呈剂量和时间依赖性降低，但两种细胞之间没有明显差异。GN-Se联合应用对基质金属蛋白酶-2的抑制作用最强。总体而言，没有一种治疗方式对正常前列腺上皮细胞有任何明显的抑制作用。本研究的数据表明，Gn-Se联合治疗可能具有化学预防价值和/或可能独立于激素状态而辅助前列腺癌的标准治疗。基质金属蛋白酶-2在癌细胞中的表达与肿瘤的侵袭转移密切相关。
The prognosis for patients with metastasized prostate cancer is still poor, despite conventional aggressive therapeutic modalities. Several in vitro studies together with animal models and epidemiological studies have indicated that phytochemicals can be antitumorigenic and may be protective against human cancers. However, the potential antitumor effects of genistein isoflavone, a widely studied nutrient phytochemical, have been equivocal. In this study, we investigated the effects of genistein-selenium (Gn-Se) combination on chemosensitivity and matrix metalloproteinase-2 (MMP-2) expression levels in PC3 (hormone-independent) and LNCaP (hormone-dependent) prostate cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium staining and ATP bioassay showed that genistein, selenium, and Gn-Se combination significantly inhibited growth of LNCaP and PC3 cells in a dose- and time-dependent manner, independent of hormonal status, and with no significant differences in chemosensitivity between LNCaP and PC3. Gn-Se combination induced significantly the greatest growth inhibition in both cell lines. Growth inhibition was through apoptosis induction. The treatment-induced apoptotic cascades are caspase-dependent, with evidence of an alternative non-caspase pathway(s). Treatment also induced a dose- and time-dependent decrease in MMP-2 expression levels in PC3 and LNCaP with no significant differences between the two cells. Gn-Se combination induced the greatest depression in MMP-2. Overall, none of the treatment modalities had any significant inhibitory effect in normal prostate epithelial cells. The data obtained from the present study indicate that Gn-Se combination may have chemopreventive value and/or may be adjuvant to standard therapy for prostate tumors independent of hormonal status. MMP-2 expression in cancer cells has been associated with active invasion and metastasis.