期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 24, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2019.102124
关键词
Cancer; Cancer stem cells; Doxorubicin; Drug resistance; Triple negative breast cancer; Pluronic; Poloxamer
资金
- National Institutes of Health [CA89225, CA151652, CA184088, CA144027]
- Department of Defense [W81XWH-11-1-0171]
The potency of polymeric micelle-based doxorubicin, SP1049C, against cancer stem cells (CSCs) in triple negative breast cancer (TNBC) is evaluated. CSCs with high epithelial specific antigen (ESA), high CD44 and low CD24 expression levels were derived from the TNBC cancer cells, MDA-MB-231 and MDA-MB-468. These CSCs were resistant to free doxorubicin (Dox) and displayed increased colony formation, migration, and invasion in vitro, along with higher tumorigenicity in vivo, compared to the parental and non-CSCs counterparts. SP1049C downregulated the expression and inhibited the functional activity of the breast cancer resistance protein (BCRP/ABCG2) in CSCs. The polymeric micelle drug had higher cytotoxicity and potency in reducing the colony formation of CSCs compared to the free drug. It was also more potent in inhibiting the tumor growth in the orthotopic animal tumor models derived from CSCs. These results indicate that SP1049C is active against CSCs and has potential in treating TNBC. (C) 2019 Published by Elsevier Inc.
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