通过脂质体 FOXM1 适体降低乳腺癌多柔比星耐药性：在体内外。
Reducing Doxorubicin resistance in breast cancer by liposomal FOXM1 aptamer: In vitro and in vivo.
机构信息
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
Department of Pharmaceutics, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
出版信息
Life Sci. 2020 Dec 1;262:118520. doi: 10.1016/j.lfs.2020.118520. Epub 2020 Oct 1.
AIMS
Drug resistance is one of the main obstacles in cancer chemotherapy. The forkhead box M1 (FOXM1) is a transcription factor and its overexpression in breast cancer is related to resistance to chemotherapy. In this study, we prepare liposomal FOXM1 aptamer (Lip-FOXM1apt) and evaluate its effects on Doxorubicin (Dox) resistance in vitro and in vivo.
MAIN METHODS
MTT assay, cell association, cellular uptake, Annexin V-FITC/PI dual staining assay were investigated in MDA-MB-231, MCF-7, 4T1. In vivo studies were performed in 4T1 tumor-bearing BALB/c mice.
KEY FINDINGS
We found that the combination therapy of Dox and Lip-FOXM1apt significantly increases both Dox cytotoxicity on cancer cells as well as Dox-induced apoptosis. Administering Lip-FOXM1apt remarkably improved the anti-tumor efficacy of Dox in mice model that was strikingly more effective than Dox monotherapy.
SIGNIFICANCE
Taken together, this study provides a new strategy to overcome Dox resistance and merits further investigation.
目的
耐药性是癌症化疗的主要障碍之一。叉头框 M1（FOXM1）是一种转录因子，其在乳腺癌中的过表达与化疗耐药性有关。在本研究中，我们制备了脂质体 FOXM1 适体（Lip-FOXM1apt），并评估了其在体外和体内对多柔比星（Dox）耐药性的影响。
主要方法
在 MDA-MB-231、MCF-7、4T1 中进行 MTT 测定、细胞结合、细胞摄取、Annexin V-FITC/PI 双重染色测定。在 4T1 荷瘤 BALB/c 小鼠中进行体内研究。
主要发现
我们发现 Dox 和 Lip-FOXM1apt 的联合治疗显著增加了癌症细胞对 Dox 的细胞毒性以及 Dox 诱导的细胞凋亡。给予 Lip-FOXM1apt 可显著提高 Dox 在小鼠模型中的抗肿瘤疗效，比 Dox 单药治疗更有效。
意义
综上所述，本研究为克服 Dox 耐药性提供了一种新策略，值得进一步研究。
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