前列腺癌是导致男性癌症死亡的主要原因。多西他赛（Doc）是一种常用的治疗方法，但由于药物毒性和耐药性，一些患者反应不佳。 Morusin 是一种在 Morus alba 中发现的异戊二烯化类黄酮，具有很强的抗癌特性。本研究的目的是研究 Morusin 和多西紫杉醇对前列腺癌细胞的联合作用，同时探讨其潜在机制。使用磺基罗丹明-B (SRB) 测定评估桑菌素、多西紫杉醇及其组合对 PC3 细胞的 IC50 值。此外，还检测了多种标记物，包括谷胱甘肽 (GSH)、丙二醛 (MDA)、炎症介质（IL-6、TNF-α、NF-κB 和 IL-10）、NQO1、NRF2 和凋亡标记物（Bax 和 Bcl2）。评价。 Morusin 和 Doc 共同给药显着降低了 Doc IC50 值，表明细胞毒性增强。联合疗法通过增加 IL-6 水平并降低升高的 TNF-α 和 NF-κB 水平来影响炎症介质。此外，该组合还降低了 GSH 水平，并提高了 MDA、NQO1 和 NRF2 水平，这些水平在细胞对氧化应激的反应中发挥着至关重要的作用。此外，morusin 通过增加 Bax 水平和减少 Bcl-2 表达来增强 Doc 诱导的细胞凋亡。分子对接分析证实桑菌素对所研究的靶蛋白具有活性。总之，桑蚕素和多西紫杉醇的组合在较低的药物浓度下显示出增强的治疗前列腺癌的功效。联合疗法可以通过调节炎症介质和调节抗氧化标志物来降低耐药性。这项研究的结果表明 Morusin 有可能成为前列腺癌的补充治疗选择。版权所有 © 2024 作者。由 Elsevier Masson SAS 出版。保留所有权利。

Prostate cancer stands as a prominent contributor to male mortality in cancer cases. Docetaxel (Doc) is a commonly used treatment, but some patients do not respond well due to drug toxicity and resistance. Morusin, a prenylated flavonoid found in Morus alba, show strong anticancer properties. The aim of this study was to investigate the combined effect of morusin and docetaxel on prostate cancer cells, while exploring the underlying mechanisms. The IC50 values of morusin, docetaxel, and their combination on PC3 cells were evaluated using the sulforhodamine-B (SRB) assay. In addition, various markers including glutathione (GSH), malondialdehyde (MDA), inflammatory mediators (IL-6, TNF-α, NF-κB, and IL-10), NQO1, NRF2, and apoptotic markers (Bax and Bcl2) were evaluated. Co-administration of morusin and Doc significantly reduced Doc IC50 value, indicating enhanced cytotoxicity. The combination therapy affected inflammatory mediators by increasing IL-6 levels and reducing elevated TNF-α and NF-κB levels. Furthermore, the combination reduced GSH levels and augmented MDA, NQO1 and NRF2 levels, which have a crucial role in the cellular response to oxidative stress. Moreover, morusin enhanced apoptosis induced by Doc through increasing Bax levels and decreasing Bcl-2 expression. Molecular docking analyses confirmed morusins' activity against the target proteins studied. In conclusion, the combination of morusin and docetaxel showed enhanced efficacy at lower drug concentrations in treating prostate cancer. The combination therapy may reduce drug resistance by modulating inflammatory mediators and regulating antioxidant markers. The results of this study indicate the possibility of morusin in being a supplementary treatment option for prostate cancer.Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.