阿霉素/泊洛沙姆聚合物胶束消除三阴性乳腺癌中的肿瘤干细胞。
Eradication of cancer stem cells in triple negative breast cancer using doxorubicin/pluronic polymeric micelles.
机构信息
Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA.
Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, USA.
出版信息
Nanomedicine. 2020 Feb;24:102124. doi: 10.1016/j.nano.2019.102124. Epub 2019 Nov 20.
Abstract
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.
摘要
评估了基于聚合物胶束的多柔比星（SP1049C）对三阴性乳腺癌（TNBC）中的癌症干细胞（CSC）的效力。从 TNBC 癌细胞 MDA-MB-231 和 MDA-MB-468 中获得了具有高上皮特异性抗原（ESA）、高 CD44 和低 CD24 表达水平的 CSC。与亲本和非 CSC 相比，这些 CSC 对游离多柔比星（Dox）具有抗性，并显示出体外集落形成、迁移和侵袭能力增强，体内致瘤性增强。SP1049C 下调了 CSC 中乳腺癌耐药蛋白（BCRP/ABCG2）的表达并抑制了其功能活性。与游离药物相比，聚合物胶束药物对 CSC 的集落形成具有更高的细胞毒性和效力。它在抑制源自 CSC 的原位动物肿瘤模型中的肿瘤生长方面也更有效。这些结果表明 SP1049C 对 CSC 具有活性，并有潜力治疗 TNBC。
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