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已发表论文
乌心石内酯 (Micheliolide) 通过谷胱甘肽 (glutathione) 下调克服在 KLF4 调节下所产生的乳腺癌细胞的顺铂 (cisplatin) 耐药性
Authors Jia Y, Zhang C, Zhou L, Xu H, Shi Y, Tong Z
Received 15 May 2015
Accepted for publication 30 July 2015
Published 28 August 2015 Volume 2015:8 Pages 2319—2327
DOI http://dx.doi.org/10.2147/OTT.S88661
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Jia Fan
Peer reviewer comments 3
Editor who approved publication: Dr Faris Farassati
Abstract: Micheliolide (MCL) is a promising novel compound with broad-spectrum anticancer activity. However, little is known regarding its action and mechanism in breast cancer. To explore the potential therapeutic application of MCL as a chemosensitivity modulator, this study investigated the effects of MCL on cisplatin sensitivity in breast cancer and the underlying mechanisms. In the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay and a xenograft tumor model, MCL enhanced the cisplatin sensitivity of the breast cancer cell line MCF-7 both in vitro and in vivo. Treatment of MCF-7 cells with low-dose cisplatin (10 µM) was sufficient to enrich the proportion of ALDH+ cells and upregulate Krüppel-like factor 4 (KLF4) expression. The results obtained from knockdown and overexpression experiments demonstrate that KLF4 is both necessary and sufficient to induce a cisplatin resistance phenotype in breast cancer cells. Furthermore, the glutathione (GSH) content was elevated in MCF-7 cells after overexpression of KLF4. KLF4-mediated resistance to cisplatin was found to be abrogated by treatment with buthionine sulfoximine, an inhibitor of GSH synthesis. MCL induced GSH depletion and severe cell death in KLF4-overexpressing MCF-7 cells following exposure to cisplatin. Therefore, these results suggest that MCL-mediated direct depletion of GSH represents a major mechanism in reversing KLF4-induced cisplatin resistance in MCF-7 cells.
Keywords: KLF4, cisplatin resistance, glutathione, breast cancer, Micheliolide
Keywords: KLF4, cisplatin resistance, glutathione, breast cancer, Micheliolide
