Department of Breast and Thyroid Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
Department of Geriatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
IUBMB Life. 2018 Jun;70(6):491-500. doi: 10.1002/iub.1749. Epub 2018 Apr 10.
In the study, we probed into the effect of Resveratrol (RES) on Doxorubicin (DOX)-resistant breast neoplasm cell line MCF-7/DOX as well as the mechanism of RES underlying the DOX-resistant breast cancer. CCK-8 assay was utilized to assess the survival rates and sensitivity of breast neoplasm cell lines MCF-7 or MDA-MB-231 to DOX and RES. DOX-resistant MCF-7 cell line was successfully cultivated with DOX dose increasing and was named MCF-7/DOX. Afterwards, wound healing and Transwell assays were performed to measure the migration and invasion capabilities of MCF-7/DOX cells, while cell propagation and apoptosis were determined by colony formation assay and flow cytometry analysis. Both western blotting and immunohistochemistry were conducted to examine the expression of proteins involved in PI3K/Akt signaling pathway. Nude mice xenograft model was constructed to further verify the effects of DOX and RES on breast neoplasm in vivo. RES restored DOX sensitivity in MCF-7/DOX cells, inhibiting biological functions of MCF-7/DOX cells and promoting cell apoptosis in vitro and impeding tumor growth in vivo. It was revealed by the mechanistic studies that MCF-7/DOX cells could regain the drug sensibility with RES treatment through inactivating the PI3K/Akt signal transduction pathway. RES could reverse DOX resistance in breast neoplasm cells and inhibited DOX-resistant breast cancer cell propagation and metastasis and facilitated cell apoptosis by modulating PI3K/Akt signaling pathway. © 2018 IUBMB Life, 70(6):491-500, 2018.
在这项研究中，我们探讨了白藜芦醇（RES）对阿霉素（DOX）耐药乳腺癌细胞系 MCF-7/DOX 的作用以及 RES 逆转 DOX 耐药乳腺癌的机制。CCK-8 法检测 MCF-7 或 MDA-MB-231 乳腺癌细胞系对 DOX 和 RES 的存活率和敏感性。通过增加 DOX 剂量成功培养 DOX 耐药 MCF-7 细胞系，并将其命名为 MCF-7/DOX。随后，通过划痕愈合和 Transwell 实验检测 MCF-7/DOX 细胞的迁移和侵袭能力，通过集落形成实验和流式细胞术分析检测细胞增殖和凋亡。采用 Western blot 和免疫组化检测参与 PI3K/Akt 信号通路的蛋白表达。构建裸鼠异种移植模型进一步验证 DOX 和 RES 对体内乳腺癌的作用。RES 恢复 MCF-7/DOX 细胞对 DOX 的敏感性，抑制 MCF-7/DOX 细胞的生物学功能，促进细胞凋亡，并抑制体内肿瘤生长。通过机制研究表明，RES 通过抑制 PI3K/Akt 信号转导通路可使 MCF-7/DOX 细胞恢复药物敏感性。RES 可通过调节 PI3K/Akt 信号通路逆转乳腺癌细胞的 DOX 耐药性，抑制 DOX 耐药乳腺癌细胞的增殖和转移，促进细胞凋亡。IUBMB Life，2018，70（6）：491-500，2018。
