Genistein treatment effects upin human prostate

Prior studies support the notion that the experimental chemopreventive agent, genistein, inhibits prostate cancer (PCa) cell movement in humans and that this in turn inhibits metastatic spread, thereby preventing PCa-specific death. As many effects have been ascribed to genistein, it has been considered a non-specific agent. However, its effects are concentration-dependent, and the vast majority of studies use concentrations greater than 3 logs above those associated with dietary consumption. Genistein is found in soy, and individuals consuming soy-based diets have blood concentrations of free genistein in the low nanomalar range. Using dosing guided by phase I pharmacokinetic studies in US men, prospective treatment of men on a phase II trial with genistein for one month prior to radical prostatectomy for localized PCa. Here we conducted an unbiased screening for effects of genistein in prostate as well as evaluate changes between normal and cancer cells. To evaluate the performance of LCM coupled to linear amplification and array-based gene profiling across multiple patient samples, normal prostate epithelial cells (N) to prostate cancer cells (T) in prostate tissue from individuals who had undergone radical prostatectomy for localized PCa. Evaluation of gene expression in genistein treated (NG) versus untreated control subjects (N), using tissue obtained as part of a prospective pre-prostatectomy trial. These studies focused upon normal prostate epithelial cells. This population of cells is present in a cancer containing gland, representing an at risk population and constitutes an important target cell population for pharmacologic targeting with chemoprevention agents. Three-condition experiment, N vs. T samples and N vs. NG. No biological replicates samples: 14 N, 10 T, and 10 NG. In total 17 slides were used.

既往研究证实，实验性化学预防剂染料木黄酮（genistein）可抑制人体前列腺癌细胞（Prostate Cancer, PCa）的运动能力，进而阻断肿瘤转移扩散，最终降低前列腺癌特异性死亡率。由于染料木黄酮被报道具有多种生物学效应，其曾被认为是一类非特异性制剂。然而，该药物的生物学效应呈浓度依赖性，且绝大多数相关研究所使用的药物浓度，较人群膳食摄入时的血液游离染料木黄酮浓度高出3个数量级以上。

染料木黄酮天然存在于大豆中，采用大豆类膳食的个体，其血液中游离染料木黄酮的浓度处于低纳摩尔级别。研究团队基于美国男性人群的I期药代动力学研究结果优化给药方案，在一项II期临床试验中，对拟接受局限性前列腺癌根治性前列腺切除术的患者，术前给予为期1个月的染料木黄酮干预治疗。

本研究对染料木黄酮在前列腺组织中的效应开展了无偏倚筛选，并对比了正常前列腺细胞与癌细胞的基因表达差异。为评估激光捕获显微切割（Laser Capture Microdissection, LCM）结合线性扩增与基于基因芯片的表达谱分析在多患者样本中的应用效能，本研究采集了接受局限性前列腺癌根治术患者的前列腺组织，从中分离正常前列腺上皮细胞（N）与前列腺癌细胞（T）。

同时利用前述术前预试验获取的组织样本，对比了染料木黄酮干预组（NG）与未干预对照组（N）的基因表达差异。本研究聚焦于正常前列腺上皮细胞：这类细胞存在于含癌腺体微环境中，属于癌症易感细胞群，同时也是化学预防药物靶向干预的重要靶细胞群体。

本实验为三条件设计，包含两组比较：N与T样本组、N与NG样本组。本次实验未设置生物学重复样本，共纳入14份N样本、10份T样本与10份NG样本，总计使用17张组织切片。