文章基本信息

标题：Mithramycin A suppresses basal triple-negative breast cancer cell survival partially via down-regulating Krüppel-like factor 5 transcription by Sp1
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作者：Rong Liu ; Xu Zhi ; Zhongmei Zhou 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：1138
DOI：10.1038/s41598-018-19489-6
语种：English
出版社：Springer Nature
摘要：As the most malignant breast cancer subtype, triple-negative breast cancer (TNBC) does not have effective targeted therapies clinically to date. As a selective Sp1 inhibitor, Mithramycin A (MIT) has been reported to have anti-tumor activities in multiple cancers. However, the efficacy and the mechanism of MIT in breast cancer, especially TNBC, have not been studied. In this study, we demonstrated that MIT suppressed breast cancer cell survival in a dosage-dependent manner. Interestingly, TNBC cells were more sensitive to MIT than non-TNBC cells. MIT inhibited TNBC cell proliferation and promoted apoptosis in vitro in time- and dosage-dependent manners. MIT suppressed TNBC cell survival, at least partially, by transcriptionally down-regulating KLF5, an oncogenic transcription factor specifically expressed in basal TNBC. Finally, MIT suppressed TNBC cell growth in a xenograft mouse model. Taken together, our findings suggested that MIT inhibits basal TNBC via the Sp1/KLF5 axis and that MIT may be used for TNBC treatment.