金雀异黄素结合硒共同诱导前列腺癌细胞的生长抑制_阿尔贝托 - 金转停_金雀异黄素Genistein

针对病种：前列腺癌

发表时间：2010年8月

发表国家：美国

登载刊物：养生膳食杂志

研究单位：美国佛罗里达大西洋大学生物科学、化学与生物化学系

研究人员：阿尔贝托海希斯，米歇尔约翰逊等

主要结论：染料木黄酮，硒，和Gn-Se 的组合可以明显抑制LNCaP 和 PC3 细胞按照剂量和时间依赖性方式的增长，并且LNCaP 和 PC3 之间的药敏试验无显著差异.

Journal of Medicinal Food, 2010, 13(4):842-50.

Genistein-selenium combination induces growth arrest in prostate cancer cells

Alberto Haces, Michelle Johnson, et al

Departments of Biological Sciences and Chemistry and Biochemistry, Florida Atlantic University, Davie, Florida, USA

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.

美国《养生膳食杂志》，2010年8月

金雀异黄素结合硒共同诱导前列腺癌细胞的生长抑制

阿尔贝托海希斯，米歇尔约翰逊等

美国佛罗里达大西洋大学生物科学、化学与生物化学系

除了常规侵略性的治疗方式，转移性前列腺癌患者的预后诊断仍然贫乏。几项体外和动物模型的研究和流行病学研究已经表明，植物化学物质具有抗肿瘤的性质，可以对抗人类癌症。然而，金雀异黄素作为一种被广泛研究的植物化学成分，其潜在的抗肿瘤作用一直模棱两可。在此研究中，我们探究了金雀异黄素-硒 (Gn-Se) 组合在PC3 （激素独立型）和 LNCaP （激素依赖型）前列腺癌细胞中对药物敏感性和基质金属蛋白酶-2 (MMP-2) 表达水平的作用。金属硫蛋白混合体染色和 ATP 生物测定表明，染料木黄酮，硒，和Gn-Se 的组合可以明显抑制LNCaP 和 PC3 细胞按照剂量和时间依赖性方式的增长，独立的荷尔蒙地位，并且LNCaP 和 PC3 之间的药敏试验无显著差异。Gn-Se 的组合在这两种细胞系中显著诱导最大程度的生长抑制。生长的抑制作用通过诱导细胞凋亡实现。由可替代的非半胱氨酸蛋白酶途径作证，这种治疗诱导细胞凋亡的通路具有半胱氨酸蛋白酶依赖性。这种治疗在 PC3 和 LNCaP细胞中也会诱导MMP-2 表达剂量和时间依赖性地减少，并且在两中细胞之间没有明显差异。Gn-Se 组合在MMP-2中诱导最严重的衰退。总体来看，没有任何治疗方式在正常前列腺上皮细胞有明显的抑制作用。目前的研究获得的数据表明 Gn-Se 组合可能有化学防癌价值和/或可能辅助独立于激素状态的前列腺肿瘤标准疗法。在肿瘤细胞中的MMP-2 表达与活性侵袭和转移有关。