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白藜芦醇在乳腺癌和前列腺癌中作用的甾体受体信号转导机制。

Steroid Receptor Signallings as Targets for Resveratrol Actions in Breast and Prostate Cancer.

机构信息

Department of Pharmacy, Health and Nutritional Sciences University of Calabria, Via Pietro Bucci, Arcavacata di Rende, 87036 Cosenza, Italy.

出版信息

Int J Mol Sci. 2019 Mar 3;20(5):1087. doi: 10.3390/ijms20051087.

Abstract

Extensive research over the past 25 years in hormone-dependent cancers, such as breast cancer and prostate cancer, has identified the molecular mechanisms driven by steroid receptors, elucidating the interplay between genomic and non-genomic steroid receptors mechanism of action. Altogether, these mechanisms create the specific gene expression programs that contribute to endocrine therapy resistance and cancer progression. These findings, on the bidirectional molecular crosstalk between steroid and growth factor receptors pathways in endocrine resistance, suggest the use of multi-target inhibitors together with endocrine therapies, for treating resistant disease. In this review we will discuss the novel understanding on the chemopreventive and anti-cancer activities of Resveratrol (3,5,4'-trihydroxy-stilbene) (RSV), a phytoalexin found in grapes acting on a plethora of targets. We will highlight Resveratrol effect on steroid receptors signalling and its potential use in the treatment of hormone-dependent cancer. Understanding the molecular mechanisms by which the bioactive compound influences cancer cell behaviour, by interfering with steroid receptors functional activity, will help to advance the design of combination strategies to increase the rate of complete and durable clinical response in patients.

摘要

在过去的 25 年中,对激素依赖性癌症(如乳腺癌和前列腺癌)的广泛研究已经确定了受类固醇受体驱动的分子机制,阐明了基因组和非基因组类固醇受体作用机制之间的相互作用。总的来说,这些机制产生了特定的基因表达程序,有助于内分泌治疗抵抗和癌症进展。这些发现表明,在激素抵抗中类固醇和生长因子受体途径的双向分子串扰,联合使用多靶点抑制剂和内分泌治疗来治疗耐药疾病。在这篇综述中,我们将讨论白藜芦醇(3,5,4'-三羟基二苯乙烯)(RSV)的新型化学预防和抗癌活性的新认识,白藜芦醇是一种在葡萄中发现的植物抗毒素,作用于众多靶点。我们将重点介绍白藜芦醇对类固醇受体信号的影响及其在激素依赖性癌症治疗中的潜在用途。了解生物活性化合物通过干扰类固醇受体功能活性影响癌细胞行为的分子机制,将有助于推进联合策略的设计,以提高患者完全和持久临床反应的速率。

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