异黄酮对前列腺癌细胞的激素受体基因表达的影响  

Influence of Isoflavones on Hormonal Receptor Gene Expression in Prostate Cancer Cells

作　　者：曹锋[1] 金泰廙[1] 周袁芬[1] 

机构地区：[1]复旦大学公共卫生学院劳动卫生与毒理学教研室国家教育部公共卫生安全重点实验室,上海200032

出　　处：《环境与职业医学》2005年第2期95-98,121,共5页Journal of Environmental and Occupational Medicine

基　　金：国家 973项目 (编号 :2 0 0 2CB51 2 90 5)

摘　　要：[目的]通过大豆异黄酮的活性物质染料木黄酮和大豆苷元抑制前列腺癌PC 3和LNCaP细胞增殖和对激素基因表达的影响,探讨大豆异黄酮治疗和预防前列腺癌的可能机制。[方法] 0、10、2 0、40、60、80和160 μmol/L剂量组的染料木黄酮和大豆苷元处理前列腺癌细胞,细胞存活率用MTT方法检测,α雌激素受体(ERα)、β雌激素受体(ERβ)、雄激素受体(AR)和血管上皮生长因子(VEGF)等基因的mRNA表达用RT PCR进行检测。[结果]染料木黄酮和大豆苷元对PC- 3、LNCaP细胞具有明显的抑制生长作用,在160 μmol/L的浓度时,染料木黄酮、大豆苷元作用72h后,PC- 3细胞的存活率分别为12 .2 8%和44 .88% ,LNCaP细胞的存活率分别为2 5 .48%和43 .14 % ,其抑制效应具有时间和剂量依赖性,同时发现对PC 3细胞的VEGF、ERα和ERβ基因表达下调,AR基因处理前后没有检测到;对LNCaP细胞的VEGF和AR基因表达下调,ERα和ERβ的表达并无影响。[结论]大豆异黄酮能抑制前列腺癌细胞的增殖效应,存在时间和剂量效应关系,雌激素受体基因可能直接在大豆苷元抑制PC 3细胞的增殖中参与作用,而染料木黄酮抑制PC- 3细胞和染料木黄酮及大豆苷元抑制LNCaP细胞可能主要是通过Akt通路影响VEGF和AR等基因而实现。Objective] To explore the possible mechanisms in terms of the viability of prostate cancer cells and the changes of hormonal gene expression after incubation with genistein and daidzein. [Methods] LNCaP cells and PC-3 cells were treated with genistein and daidzein at varying doses to evaluate viability by use of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium(MTT).Reverse transcription polymerase chain reaction(RT-PCR) was conducted to examine the level of mRNA of the hormonal receptor gene(ERα,ERβ and AR) and vascular endothelial growth factor gene(VEGF). [Results] It has been revealed that the viability for both prostate cancer cell lines decreased following increasing concentration and treatment period concurrently.The gene expression of VEGF,ERα and ERβ decreased and AR gene did not express after incubation with genistein and daidzein in PC-3 cells.In the LNCaP cells,the expression of VEGF and AR gene decreased but ERα and ERβ genes did not change after incubation with genistein and daidzein. [Conclusion] Genistein and daidzein exert a time-and dose-dependent inhibitory effects on both prostate cancer cell lines;the down-regulation expression of ERs gene induced by daidzein in PC-3 cells may influence the proliferous effect directly.However,the inhibition of PC-3 cells by genistein and the inhibition of LNCaP cells by genistein and daidzein may be caused via the pathway of Akt,then down-regulated the expression of AR and VEGF gene.

关 键 词：前列腺癌细胞 基因表达 LNCAP细胞 PC-3细胞 染料木黄酮 血管上皮生长因子 大豆异黄酮 雌激素受体基因 大豆苷元 mol/L α雌激素受体 β雌激素受体 RT-PCR mRNA表达 VEGF 剂量效应关系 表达下调 AR基因 防前列腺癌 MTT方法 

分 类 号：R737.25[医药卫生—肿瘤] R735.2[医药卫生—临床医学]