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草药化合物PC-SPES的分子效应:前列腺癌活性途径的鉴定

Molecular effects of the herbal compound PC-SPES: identification of activity pathways in prostate carcinoma.

作者信息

Bonham Michael, Arnold Hugh, Montgomery Bruce, Nelson Peter S

机构信息

Divisions of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

出版信息

Cancer Res. 2002 Jul 15;62(14):3920-4.

Abstract

Clinical trials of the herbal preparation PC-SPES have demonstrated substantial responses in patients with advanced prostate cancer. Biochemical assays and clinical observations suggest that the effects of PC-SPES are mediated at least in part through estrogenic activity, although the mechanism(s) remains largely undefined. In this study, we used cDNA microarray analysis to identify gene expression changes in LNCaP prostate carcinoma cells exposed to PC-SPES and estrogenic agents including diethylstilbestrol. PC-SPES altered the expression of 156 genes after 24 h of exposure. Of particular interest, transcripts encoding cell cycle-regulatory proteins, alpha- and beta-tubulins, and the androgen receptor were down-regulated by PC-SPES. A comparison of gene expression profiles resulting from these treatments indicates that PC-SPES exhibits activities distinct from those attributable to diethylstilbestrol and suggests that alterations in specific genes involved in modulating the cell cycle, cell structure, and androgen response may be responsible for PC-SPES-mediated cytotoxicity.

摘要

草药制剂PC-SPES的临床试验已证明对晚期前列腺癌患者有显著疗效。生化分析和临床观察表明,PC-SPES的作用至少部分是通过雌激素活性介导的,尽管其机制在很大程度上仍不明确。在本研究中,我们使用cDNA微阵列分析来鉴定暴露于PC-SPES和雌激素类药物(包括己烯雌酚)的LNCaP前列腺癌细胞中的基因表达变化。暴露24小时后,PC-SPES改变了156个基因的表达。特别值得关注的是,PC-SPES下调了编码细胞周期调节蛋白、α和β微管蛋白以及雄激素受体的转录本。对这些处理产生的基因表达谱的比较表明,PC-SPES表现出与己烯雌酚不同的活性,并表明参与调节细胞周期、细胞结构和雄激素反应的特定基因的改变可能是PC-SPES介导的细胞毒性的原因。

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