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载抗癌药物的固体脂质纳米粒逆转多药耐药癌细胞耐药性的研究。

Drug resistance reversal activity of anticancer drug loaded solid lipid nanoparticles in multi-drug resistant cancer cells.

机构信息

Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, PR China.

出版信息

Colloids Surf B Biointerfaces. 2013 Oct 1;110:74-80. doi: 10.1016/j.colsurfb.2013.03.037. Epub 2013 Apr 17.

Abstract

The aim of our study was to enhance the cytotoxicity of anticancer drugs by reversing the resistance of multi-drug resistant cancer cells. The cytotoxicities of paclitaxel (PTX) and doxorubicin (DOX), either as single agents or loaded in solid lipid nanoparticles (SLN) by a solvent diffusion method, were examined using drug sensitive cancer cells and drug resistant cells by measuring the drug concentration required for 50% growth inhibition (IC50). Compared to Taxol and DOX·HCl solution, both PTX and DOX loaded in SLN exhibited higher cytotoxicities in human breast tumor drug sensitive MCF-7 and drug resistant MCF-7/ADR cells. The ability of PTX loaded SLN and DOX loaded SLN to reverse the drug resistance of MCF-7 cells compared to MCF-7/ADR cells was 31.0 and 4.3 fold, respectively. Both PTX and DOX loaded SLN showed the same trends of enhanced cytotoxicity against a second wild type/drug resistant human ovarian cancer cell pair SKOV3 and SKOV3-TR30 cells. The reversal powers were 3.8 and 1.9 fold for PTX loaded SLN and DOX loaded SLN, respectively.

摘要

本研究旨在通过逆转多药耐药癌细胞的耐药性来增强抗癌药物的细胞毒性。采用溶剂扩散法将紫杉醇(PTX)和阿霉素(DOX)分别负载于固体脂质纳米粒(SLN)中,通过测定抑制 50%细胞生长所需的药物浓度(IC50),用药物敏感癌细胞和耐药癌细胞来检测紫杉醇和阿霉素的细胞毒性。与 Taxol 和 DOX·HCl 溶液相比,负载于 SLN 中的 PTX 和 DOX 在人乳腺癌敏感 MCF-7 细胞和耐药 MCF-7/ADR 细胞中均表现出更高的细胞毒性。与 MCF-7/ADR 细胞相比,负载 PTX 的 SLN 和负载 DOX 的 SLN 逆转 MCF-7 细胞耐药的能力分别为 31.0 倍和 4.3 倍。负载 PTX 和 DOX 的 SLN 对第二种野生型/耐药型人卵巢癌细胞对 SKOV3 和 SKOV3-TR30 细胞的细胞毒性增强也呈现出相同的趋势。负载 PTX 的 SLN 和负载 DOX 的 SLN 的逆转能力分别为 3.8 倍和 1.9 倍。

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