A novel anti-cancer effect of genistein： reversal of epithelial mesenchymal transition in prostate cancer cells  

作　　者：Lin-lin ZHANG Lei LI Da-peng WU Jin-hai FAN Xiang LI Kai-jie WU Xin-yang WANG Da-lin HE 

机构地区：[1]Department of Urology, the First Affiliated Hospital of Medical School, Xi'an .liaotong University, Xi 'an 710061, China

出　　处：《Acta Pharmacologica Sinica》2008年第9期1060-1068,共9页中国药理学报（英文版）

基　　金：Project supported, m part by grants from the National Natural Science Foundation of China （No 30500502） and the National 863 project of China （No 2006AA020705）.Lin-lin ZHANG, Lei LI, and Da-lin HE designed research; Lin-lin ZHANG, Xiang LI, Kai-jie WU, and Xin- yang WANG performed research; Da-peng WU and Jin-hai FAN contributed new analytical reagents and tools; Lin- lin ZHANG and Da-lin HE analyzed data; Lin-lin ZHANG and Da-lin HE wrote the paper.

摘　　要：Aim： The aim of the present study was to investigate whether low dose genistein affects the invasion and epithelial mesenchymal transition （EMT） of prostate cancer （PCa） cells. Methods： Human PCa cell lines, IA8-ARCaP and LNCaP/ HIF-1a, were used in this study. The cell lines were found to process EMT in our previous study. The PCa cells were treated with increasing concentrations, from 0.1 to 75 pmol/L. Proliferation was assessed with 3-（4,5-dimethylthiazo1- 2-yl）-2,5-diphenyltetrazolium bromide assay. EMT was proven by cell morphological transition and the expression changes of EMT-related markers, which were confirmed by RT-PCR, Western blotting, and indirect immunofluorescence labeling. Transwell invasion assay was used to analyze the invasive potency. Results： The addition of genistein to the medium reduced the IA8-ARCaP and LNCaP/HIF-1 a viable cell number in a dose-dependent manner （with increasing concentrations from 15 to 75 μmol/L）. Less than 15 μmol/L genistein was selected as the low dose concentration, which did not affect cell proliferation. The treatment of cells with low-dose genistein induced the reversal of EMT, which was confirmed by cell morphological transition and the expression changes of EMT-related markers. The reversal of EMT in the PCa cells by low-dose genistein was in a dose-dependent manner. Moreover, low-dose genistein effectively inhibited invasion of the PCa ceils in vitro. Conclusion： These results showed that treatment with low-dose genistein may be a potential strategy for the suppression of invasive growth through the reversal of EMT in cancer cells, which justifies the potential use of soybean foods as a practical chemopreventive approach for patients with PCa.瞄准：现在的学习的目的是调查低剂量 genistein 是否影响侵略和前列腺癌症(PCa ) 的上皮的间充质的转变(EMT ) 房间。方法：人的 PCa 房间线， IA8-ARCaP 和 LNCaP/ HIF-la，在这研究被使用。房间线被发现在我们的以前的学习处理 EMT。PCa 房间与增加集中被对待，从 0.1 ～ 75 μmol/L。增长与 3-(4,5-dimethylthiazol-2-yl ) 被估计 -2,5-diphenyltetrazolium 溴化物试金。EMT 被词法转变和表示 EMT 相关的标记改变的房间证明，它被 RT-PCR 证实，西方的弄污，并且标记的间接免疫荧光。Transwell 侵略试金被用来分析侵略力量。结果：到媒介的 genistein 的增加以一种剂量依赖者方式减少了 IA8-ARCaP 和 LNCaP/HIF-la 可行房间数字(与从 15 ～ 75 μmol/L 增加集中) 。不到 15 μmol/L genistein 作为低剂量集中被选择，它没影响房间增长。有低剂量的 genistein 的房间的处理导致了 EMT 的颠倒，它被词法转变和表示 EMT 相关的标记改变的房间证实。在由低剂量的 genistein 的 PCa 房间的 EMT 的颠倒以一种剂量依赖者方式。而且，低剂量的 genistein 有效地在 vitro 禁止了 PCa 房间的侵略。结论：这些结果证明有低剂量的 genistein 的治疗可以是为通过在癌症房间的 EMT 的颠倒的侵略生长的抑制的潜在的策略，它与 PCa 为病人作为一条实际 chemopreventive 途径认为大豆食物的潜在的使用正当。

关 键 词：GENISTEIN cell invasion prostate cancer epithelial mesenchymal transition 

分 类 号：R36[医药卫生—病理学] R737.25[医药卫生—基础医学]