Department of Pharmacology, Faculty of Medicine, University of Jordan, Amman 11942, Jordan.
Genomics. 2013 Apr;101(4):213-20. doi: 10.1016/j.ygeno.2012.11.009. Epub 2012 Nov 30.
Many molecular mechanisms contribute to the development of doxorubicin resistance and different cancers can express wide and diverse arrays of drug-resistance genes. The aim of this study was to identify the changes in gene expression associated with the development of doxorubicin resistance in MCF7 breast cancer cell line. The doxorubicin resistant MCF7 cell line was developed by stepwise selection of MCF7 cells and was tested using the MTT assay. The alterations in gene expression were examined using the real-time based PCR array. The findings showed an up-regulation of many phase I/II metabolizing genes, specifically, the CYP1A1 and the CYP1A2 that were up-regulated by 206- and 96-fold respectively. Drug efflux pump genes were also up-regulated profoundly. TOP2A was strongly down-regulated by 202-fold. Many other changes were observed in genes crucial for cell cycle, apoptosis and DNA repair. The findings of this project imply that the development of doxorubicin resistance is a multi-factorial process.
许多分子机制有助于多柔比星耐药的发展，不同的癌症可以表达广泛而多样的耐药基因。本研究的目的是鉴定与 MCF7 乳腺癌细胞系多柔比星耐药发展相关的基因表达变化。通过逐步选择 MCF7 细胞，建立了多柔比星耐药 MCF7 细胞系，并通过 MTT 测定法进行了测试。使用实时定量 PCR 阵列检查了基因表达的变化。研究结果显示，许多 I/II 期代谢基因上调，特别是 CYP1A1 和 CYP1A2，分别上调 206 倍和 96 倍。药物外排泵基因也被显著上调。TOP2A 被强烈下调 202 倍。还观察到许多其他与细胞周期、细胞凋亡和 DNA 修复相关的关键基因发生了变化。本项目的研究结果表明，多柔比星耐药的发展是一个多因素的过程。
