虎杖 (Thunb.) Moldenke (Polygonum multiflorum Thunb, PM) 是一种药用植物，几个世纪以来一直是传统中医 (TCM) 的组成部分，用于治疗多种病症。最近的研究表明，PM 以 AR 依赖性方式抑制前列腺癌的生长。然而，其在治疗晚期前列腺癌中的作用和机制仍有待探索。本研究旨在探讨PM对前列腺癌的抗肿瘤作用和潜在机制。通过细胞活力、集落形成、荧光激活细胞分选（FACS）和伤口愈合实验来评估PM对前列腺癌的肿瘤抑制作用。体外致死性前列腺癌模型。建立异种移植小鼠模型，检测PM对肿瘤生长的影响并评价其体内生物安全性。应用综合网络药理学、RNA-seq 和生物信息学来确定 PM 在前列腺癌中的作用机制。通过分子对接、细胞热位移分析（CETSA）、CRISPR-Cas13、RT-qPCR和WB等技术合作鉴定了PM中潜在的抗肿瘤成分及其相应靶点。PM显着抑制了前列腺癌的生长并使其敏化。前列腺癌与 AR 拮抗剂。从机制上讲，PM 通过调节 CDK1 的磷酸化诱导 G2/M 期细胞周期停滞。此外，源自 PM 及其结构类似物的聚半乳酸通过靶向 CDC25B（控制 CDK1 磷酸化的细胞周期主调节因子）来抑制前列腺癌生长。PM 及其成分聚半乳酸通过调节 CDC25B-CDK1 轴来抑制致命的前列腺癌生长诱导细胞周期停滞。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb, PM) is a medicinal plant that was an element of traditional Chinese medicine (TCM) for centuries as a treatment for a wide range of conditions. Recent studies reported that PM suppressed prostate cancer growth in an AR-dependent manner. However, its role and mechanism in the treatment of advanced prostate cancer remain to be explored. This study aims to explore the anti-tumor role and potential mechanism of PM on prostate cancer.Cell viability, colony formation, fluorescence-activated cell sorting (FACS), and wound-healing assays were conducted to evaluate the tumor suppression effect of PM on lethal prostate cancer models in vitro. A xenograft mice model was established to detect the impact of PM on tumor growth and evaluate its biosafety in vivo. Integrative network pharmacology, RNA-seq, and bioinformatics were applied to determine the mechanisms of PM in prostate cancer. Molecular docking, cellular thermal shift assay (CETSA), CRISPR-Cas13, RT-qPCR, and WB were collaboratively employed to identify the potential anti-tumor ingredient derived from PM and its corresponding targets.PM significantly suppressed the growth of prostate cancer and sensitized prostate cancer to AR antagonists. Mechanistically, PM induced G2/M-phase cell-cycle arrest by modulating the phosphorylation of CDK1. Additionally, polygalacic acid derived from PM and its structural analog suppress prostate cancer growth by targeting CDC25B, a master regulator of the cell cycle that governs CDK1 phosphorylation.PM and its ingredient polygalacic acid suppress lethal prostate cancer growth by regulating the CDC25B-CDK1 axis to induce cell cycle arrest.Copyright © 2024 Elsevier Inc. All rights reserved.