Jones Sunita B, DePrimo Samuel E, Whitfield Michael L, Brooks James D
Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):596-604. doi: 10.1158/1055-9965.EPI-04-0398.
The transhydroxystilbene resveratrol is found at high levels in red wine and grapes, and red wine consumption may be inversely associated with prostate cancer risk. To gain insights into the possible mechanisms of action of resveratrol in human prostate cancer, we did DNA microarray analysis of the temporal transcriptional program induced by treatment of the human prostate cancer cell line LNCaP with resveratrol.
Spotted DNA microarrays containing over 42,000 elements were used to obtain a global view of the effects of resveratrol on gene expression. Prostate-specific antigen (PSA) and androgen receptor (AR) expression were determined by Northern blot and immunoblot analyses. Cell proliferation was determined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and cell cycle analysis by flow cytometry.
We observed time-dependent expression changes in >1,600 transcripts as early as 6 hours after treatment with resveratrol. Most striking was the modulation of a number of important genes in the androgen pathway including PSA and AR. Resveratrol also down-regulated expression of cell cycle and proliferation-specific genes involved in all phases of the cell cycle, induced negative regulators of proliferation, caused accumulation of cells at the sub-G1 and S phases of the cell cycle, and inhibited cell proliferation in a time- and dose-dependent manner.
Resveratrol produces gene expression changes in the androgen axis and cell cycle regulators that may underlie its putative anticancer activities in prostate cancer.
反式羟基芪白藜芦醇在红酒和葡萄中含量很高，饮用红酒可能与前列腺癌风险呈负相关。为深入了解白藜芦醇在人类前列腺癌中可能的作用机制，我们对用白藜芦醇处理人前列腺癌细胞系LNCaP所诱导的时间依赖性转录程序进行了DNA微阵列分析。
使用含有超过42,000个元件的点阵DNA微阵列来全面了解白藜芦醇对基因表达的影响。通过Northern印迹和免疫印迹分析确定前列腺特异性抗原（PSA）和雄激素受体（AR）的表达。通过3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐试验测定细胞增殖，并通过流式细胞术进行细胞周期分析。
我们观察到，在用白藜芦醇处理后最早6小时，超过1600个转录本出现时间依赖性表达变化。最显著的是雄激素途径中许多重要基因的调节，包括PSA和AR。白藜芦醇还下调了参与细胞周期所有阶段的细胞周期和增殖特异性基因的表达，诱导增殖负调节因子，导致细胞在细胞周期的亚G1期和S期积累，并以时间和剂量依赖性方式抑制细胞增殖。
白藜芦醇在雄激素轴和细胞周期调节因子中产生基因表达变化，这可能是其在前列腺癌中假定的抗癌活性的基础。
