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白藜芦醇通过抑制上皮间质转化和调节 SIRT1/β-catenin 信号通路促进阿霉素敏感性在乳腺癌中的作用。

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

机构信息

Department of Pathology, Nantong Tumor Hospital, Nantong, China.

出版信息

Cancer Med. 2019 Mar;8(3):1246-1257. doi: 10.1002/cam4.1993. Epub 2019 Jan 29.

Abstract

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.

摘要

乳腺癌是全球女性致死率较高的疾病之一,无法进行手术的患者通常依赖全身化疗来延长生存时间。阿霉素(DOX)是治疗乳腺癌最常用的化疗药物之一,但对 DOX 的获得性耐药会严重影响化疗效果,导致预后不良和癌症复发。白藜芦醇(RES)是一种具有药理抗肿瘤特性的植物抗毒素,但在治疗 DOX 耐药性乳腺癌中的作用机制尚不清楚。我们使用细胞活力测定、细胞划痕试验和 Transwell 试验,结合 Western blot 和免疫荧光染色,评估 RES 对阿霉素耐药 MCF7/ADR 乳腺癌细胞的耐药性和上皮-间充质转化(EMT)的影响,并探讨其潜在机制。结果表明,RES 联合 DOX 治疗可有效抑制细胞生长,抑制细胞迁移,促进细胞凋亡。RES 通过调节 SIRT1 和 β-连环蛋白之间的连接来逆转 MCF7/ADR 细胞的 EMT 特性,为克服 DOX 耐药性提供了有希望的治疗途径,从而延长乳腺癌患者的生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4df/6434195/82fa44a0871e/CAM4-8-1246-g001.jpg

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