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血清对(-)-棉酚抑制人前列腺癌细胞生长的影响。

Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells.

作者信息

Huang Yi-Wen, Wang Li-Shu, Chang Hsiang-Lin, Ye Weiping, Sugimoto Yasuro, Dowd Michael K, Wan Peter J, Lin Young C

机构信息

Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.

出版信息

Anticancer Res. 2006 Sep-Oct;26(5A):3613-20.

Abstract

BACKGROUND

Gossypol, a natural polyphenolic compound present in cottonseeds, possesses antiproliferative and pro-apoptotic effects in in vivo and in vitro models. There are two enantiomers, (+)-gossypol and (-)-gossypol, the latter being a more potent inhibitor of cancer cell growth. Here, the effect of bovine serum albumin (BSA) and dextran-coated charcoal-treated fetal bovine serum (DCC-FBS)-containing medium on the ability of (-)-gossypol to inhibit the growth of human prostate cancer cells was studied.

MATERIALS AND METHODS

BSA- and DCC-FBS-supplemented medium were used to examine the influence of serum proteins on the antiproliferative effects of (-)-gossypol in DU-145 cells, a human prostate cancer cell line. The viability of the DU-145 cells was determined by CellTiter 96 Aqueous assay. The expressions of mRNA and protein for the cell cycle regulators, cyclin-D1, Rb, CDK, p21 and TGF-beta, were determined by RT-PCR and Western blot analyses, respectively.

RESULTS

(-)-Gossypol caused growth suppression of the DU-145 cells. In comparison with BSA-supplemented medium, DCC-FBS blocked the antiproliferative effects of (-)-gossypol at 1 and 2.5 microM, but not at 5 microM. Furthermore, (-)-gossypol treatment down-regulated cyclin-D1, Rb, CDK4 and CDK6, and up-regulated p21 and TGF-beta1 at the mRNA and/or protein levels.

CONCLUSION

The data suggested that (-)-gossypol-suppressed prostate cancer cell growth may be influenced through cell cycle regulators, which may lead to better prognosis. We further speculate that (-)-gossypol might serve as a chemotherapeutic agent for human prostate cancer patients.

摘要

背景

棉酚是一种存在于棉籽中的天然多酚化合物,在体内和体外模型中具有抗增殖和促凋亡作用。它有两种对映体,(+)-棉酚和(-)-棉酚,后者是更有效的癌细胞生长抑制剂。在此,研究了含牛血清白蛋白(BSA)和葡聚糖包被活性炭处理的胎牛血清(DCC-FBS)的培养基对(-)-棉酚抑制人前列腺癌细胞生长能力的影响。

材料与方法

使用补充了BSA和DCC-FBS的培养基来检测血清蛋白对人前列腺癌细胞系DU-145中(-)-棉酚抗增殖作用的影响。通过CellTiter 96 Aqueous检测法测定DU-145细胞的活力。分别通过RT-PCR和蛋白质印迹分析测定细胞周期调节因子细胞周期蛋白D1、Rb、细胞周期蛋白依赖性激酶(CDK)、p21和转化生长因子-β(TGF-β)的mRNA和蛋白表达。

结果

(-)-棉酚导致DU-145细胞生长受到抑制。与补充了BSA的培养基相比,DCC-FBS在1 microM和2.5 microM浓度下阻断了(-)-棉酚的抗增殖作用,但在5 microM浓度下未阻断。此外,(-)-棉酚处理在mRNA和/或蛋白水平下调了细胞周期蛋白D1、Rb、CDK4和CDK6,并上调了p21和TGF-β1。

结论

数据表明,(-)-棉酚抑制前列腺癌细胞生长可能是通过细胞周期调节因子实现的,这可能导致更好的预后。我们进一步推测,(-)-棉酚可能作为人类前列腺癌患者的化疗药物。

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