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Mifepristone Derivative FZU-00,003 Suppresses Triple-negative Breast Cancer Cell Growth partially via miR-153-KLF5 axis

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机构： [1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, China. [2]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, PR China. [3]College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China. [4]Department of Breast Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650118, China. [5]Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. [6]Key Laboratory of Breast Cancer in Shanghai, Cancer Institute, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China. [7]Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. [8]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

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Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers lacking targeted therapeutics currently. We recently reported that mifepristone (MIF), a drug regularly used for abortion, suppresses TNBC cell growth by inhibiting KLF5 expression via inducing miR-153. However, its anticancer efficacy is only modest at high dose. In order to enhance the anticancer activities, a focused compound library containing 17 compounds by altering the sensitive metabolic region of mifepristone has been designed and synthesized. We first tested the cell growth inhibitory effects of these compounds in TNBC cell lines. Among them, FZU-00,003 displayed the most potent efficiency. FZU-00,003 suppresses TNBC cell growth, cell cycle progression and induces apoptosis more effectively than MIF does. Consistently, FZU-00,003 induces miR-153 expression and suppressed KLF5 expression at much lower dosages than MIF does. Furthermore, FZU-00,003 inhibits tumor growth more potently than MIF does. Taken together, the MIF derivative, FZU-00,003 may serve as a better therapeutic compound for TNBC than MIF.© The author(s).

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出版当年[2020]版：

大类 | 2 区生物

小类 | 3 区生化与分子生物学

最新[2023]版：

大类 | 2 区

生物学

小类 | 2 区生化与分子生物学

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出版当年[2019]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

最新[2023]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 8.2 最新[2023版] 8.3 最新五年平均 4.858 出版当年[2019版] 4.915 出版当年五年平均 4.067 出版前一年[2018版] 6.582 出版后一年[2020版]

第一作者：

第一作者机构： [1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, China. [2]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, PR China.

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通讯作者：

通讯机构： [1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, China. [8]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.

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