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载维生素D纳米结构脂质载体(NLC):提高阿霉素治疗乳腺癌疗效的新策略。

Vitamin D-Loaded Nanostructured Lipid Carrier (NLC): A New Strategy for Enhancing Efficacy of Doxorubicin in Breast Cancer Treatment.

作者信息

Sabzichi Mehdi, Mohammadian Jamal, Mohammadi Maryam, Jahanfar Farhad, Movassagh Pour Ali Akbar, Hamishehkar Hamed, Ostad-Rahimi Alireza

机构信息

a Drug Applied Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.

b Hematology Oncology Research Center , Tabriz University of Medical Sciences , Tabriz , Iran.

出版信息

Nutr Cancer. 2017 Aug-Sep;69(6):840-848. doi: 10.1080/01635581.2017.1339820. Epub 2017 Jul 25.

Abstract

The dangerous dose-dependent side effects of anticancer agents triggered the finding of new approaches for elevated chemotherapy efficacy. This study investigated the potential application of nanostructured lipid careers (NLCs) in increasing vitamin D (VitD) effectiveness in breast cancer cell (MCF-7) in concurrent administration with doxorubicin (Dox). VitD-loaded NLCs were characterized by particle size, zeta potential, Fourier transform infrared spectroscopy, and scanning electron microscope. Cytotoxicity and molecular effects of formulation were evaluated by MTT, DAPI staining, flow cytometry, and real-time quantitative PCR assays. The formulation revealed mean particle size of 87±5 nm with a polydispersity index of 0.24 confirmed by SEM images. The IC values for VitD and Dox were 1.3 ± 0.04 and 0.65 ± 0.05 µM, respectively. VitD-loaded NLCs decreased the percentage of cell proliferation from 49 ± 7.2% to 37 ± 5.1% (P < 0.05). Cotreatment of the cells with VitD-loaded NLCs and Dox caused over a twofold increase in the percentage of apoptosis (P < 0.05). Gene expression profile demonstrated a significant decrease in antiapoptotic factor survivin along with increase in proapoptotic factor Bax mRNA levels. Overall, our results introduced the NLC technology as a novel strategy to elevate the efficacy of chemotherapeutics in breast cancer.

摘要

抗癌药物危险的剂量依赖性副作用促使人们寻找提高化疗疗效的新方法。本研究调查了纳米结构脂质载体(NLCs)在与阿霉素(Dox)联合给药时提高维生素D(VitD)对乳腺癌细胞(MCF-7)有效性方面的潜在应用。通过粒径、zeta电位、傅里叶变换红外光谱和扫描电子显微镜对负载VitD的NLCs进行了表征。通过MTT、DAPI染色、流式细胞术和实时定量PCR分析评估了制剂的细胞毒性和分子效应。SEM图像证实该制剂的平均粒径为87±5nm,多分散指数为0.24。VitD和Dox的IC值分别为1.3±0.04和0.65±0.05µM。负载VitD的NLCs使细胞增殖百分比从49±7.2%降至37±5.1%(P<0.05)。负载VitD的NLCs与Dox联合处理使细胞凋亡百分比增加了两倍多(P<0.05)。基因表达谱显示抗凋亡因子survivin显著降低,同时促凋亡因子Bax mRNA水平升高。总体而言,我们的结果表明NLC技术是提高乳腺癌化疗疗效的一种新策略。

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