Effective treatment of drug resistant recurrent breast tumors harboring cancer stem-like cells by staurosporine/epirubicin co-loaded polymeric micelles
Effective treatment of drug resistant recurrent breast tumors harboring cancer stem-like cells by staurosporine/epirubicin co-loaded polymeric micelles
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DOI：
10.1016/j.jconrel.2017.08.025
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发表时间：
2017-10-28
影响因子：
10.8
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
--
作者：
Zhang, Juanjuan;Kinoh, Hiroaki;Kataoka, Kazunori
乳腺癌复发和耐药与肿瘤干细胞亚群有关。由于传统疗法不能治疗CSCs，因此制定能够根除癌细胞和CSCs的新的治疗策略是实现有效治疗和长期生存的核心。在这里，我们研究了协同负载细胞毒性药物表阿霉素(Epi)和CSC抑制剂星形孢子素(STS)的聚合物胶束治疗乳腺肿瘤的能力，特别是当肿瘤在化疗后复发时。STS/EPI/m胶束(STS/Epi/m)对初治的原位4T1-Luc乳腺肿瘤和复发的Epi耐药乳腺肿瘤均显示出有效的治疗效果，显著延长了生存期。STS/Epi/m的这种药效增强与胶束抑制乳腺癌相关的CSC亚群的能力有关，即EPi耐药细胞和肿瘤中的乙醛脱氢酶(ALDH(+))亚群和CD44(+)/CD24-组分。这些结果表明，STS/Epi/m是一种有希望的乳腺癌有效治疗策略。
Breast cancer recurrence and resistance are associated with cancer stem-like cell (CSC) sub-populations. As conventional therapies fail to treat CSCs, institution of novel therapeutic strategies capable of eradicating both cancer cells and CSCs is central for achieving effective treatments with long-term survival. Here, we studied the ability of polymeric micelles cooperatively loading the cytotoxic drug epirubicin (Epi) and the CSC inhibitor staurosporine (STS) to treat breast tumors, particularly when tumors relapsed after chemotherapy. The STS/Epiloaded micelles (STS/Epi/m) demonstrated potent therapeutic efficacy against both naive orthotopic 4T1-luc breast tumors and their recurrent Epi-resistant counterparts, significantly prolonging survival. This efficacy enhancement of STS/Epi/m was correlated with the ability of the micelles to suppress the CSC-associated sub-populations of breast cancer, i.e. the aldehyde dehydrogenase-positive (ALDH(+)) population and the CD44(+)/CD24-fraction, in Epi-resistant cells and tumors. These results demonstrated STS/Epi/m as a promising strategy for effective management of breast cancer.