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Resveratrol promotes sensitization to Doxorubicin by inhibiting epithelial‐mesenchymal transition and modulating SIRT1/β‐catenin signaling pathway in breast cancer

机译:白藜芦醇通过抑制上皮-间质转化并调节乳腺癌的SIRT1 /β-catenin信号通路来促进对阿霉素的敏感性

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摘要

Breast cancer is one of the leading fatal diseases for women worldwide who cannot have surgery typically have to rely on systemic chemotherapy to extend their survival. Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents against breast cancer, but acquired resistance to DOX can seriously impede the efficacy of chemotherapy, leading to poor prognosis and recurrences of cancer. Resveratrol (RES) is a phytoalexin with pharmacological antitumor properties, but its underlying mechanisms are not clearly understood in the treatment of DOX‐resistant breast cancer. We used cell viability assays, cell scratch tests, and transwell assays combined with Western blotting and immunofluorescent staining to evaluate the effects of RES on chemoresistance and the epithelial‐mesenchymal transitions (EMTs) in adriamycin‐resistant MCF7/ADR breast cancer cells, and to investigate its underlying mechanisms. The results showed that a treatment of RES combining with DOX effectively inhibited cell growth, suppressed cell migration, and promoted cell apoptosis. RES reversed EMT properties of MCF7/ADR cells by modulating the connection between SIRT1 and β‐catenin, which provides a hopeful therapeutic avenue to conquer DOX‐resistance and thereby prolong survival rates in breast cancer patients.
机译:乳腺癌是全世界无法手术的妇女的主要致命疾病之一,通常必须依靠全身化疗来延长其生存期。阿霉素(DOX)是最常用的抗乳腺癌化疗药物之一,但获得的对DOX的耐药性会严重阻碍化学疗法的疗效,从而导致不良的预后和癌症复发。白藜芦醇(RES)是一种具有药理抗肿瘤特性的植物抗毒素,但在抗DOX的乳腺癌治疗中尚不清楚其潜在机制。我们使用细胞活力分析,细胞划痕测试和Transwell分析结合Western印迹和免疫荧光染色来评估RES对耐阿霉素MCF7 / ADR乳腺癌细胞化学耐药性和上皮间质转化(EMT)的影响,并调查其潜在机制。结果表明,RES与DOX联合使用可有效抑制细胞生长,抑制细胞迁移并促进细胞凋亡。 RES通过调节SIRT1和β-catenin之间的联系来逆转MCF7 / ADR细胞的EMT特性,这为征服DOX耐药性并延长乳腺癌患者的生存率提供了希望的治疗途径。

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