Middle East Technical University, Department of Biological Sciences, 06531, Ankara, Turkey.
Eur J Pharmacol. 2011 Apr 25;657(1-3):4-9. doi: 10.1016/j.ejphar.2011.02.001. Epub 2011 Feb 18.
Resistance to the broad spectrum of chemotherapeutic agents in cancer cell lines and tumors has been called multiple drug resistance (MDR). In this study, the molecular mechanisms of resistance to two anticancer agents (paclitaxel and vincristine) in mammary carcinoma cell line MCF-7 were investigated. Drug resistant sublines to paclitaxel (MCF-7/Pac) and vincristine (MCF-7/Vinc) that were developed from sensitive MCF-7 cells (MCF-7/S) were used. cDNA microarray analysis was performed for the RNA samples of sensitive and resistant cells in duplicate experiments. GeneSpring GX 7.3.1 Software was used in data analysis. The results indicated that the upregulation of MDR1 gene is the dominating mechanism of the paclitaxel and vincristine drug resistance. Additionally the upregulation of the genes encoding the detoxifying enzymes (i.e. GSTP1) was observed. Significant downregulation of apoptotic genes (i.e. PDCD2/4/6/8) and upregulation of some cell cycle regulatory genes (CDKN2A, CCNA2 etc.) was seen which may be in close relation to MDR in breast cancer. Drug resistant cancer cells exhibit different gene expression patterns depending on drug treatment, and each drug resistance phenotype is probably genetically different. Further functional studies are needed to demonstrate the complete set of genes contributing to the drug resistance phenotype in breast cancer cells.
癌细胞系和肿瘤对广谱化疗药物的耐药性被称为多药耐药（MDR）。在这项研究中，我们研究了乳腺癌细胞系 MCF-7 对两种抗癌药物（紫杉醇和长春新碱）耐药的分子机制。从敏感 MCF-7 细胞（MCF-7/S）中开发出了对紫杉醇（MCF-7/Pac）和长春新碱（MCF-7/Vinc）耐药的亚系（MCF-7/Pac 和 MCF-7/Vinc）。在重复实验中，对敏感和耐药细胞的 RNA 样本进行了 cDNA 微阵列分析。使用 GeneSpring GX 7.3.1 软件进行数据分析。结果表明，MDR1 基因的上调是紫杉醇和长春新碱耐药的主要机制。此外，还观察到解毒酶（如 GSTP1）编码基因的上调。凋亡基因（如 PDCD2/4/6/8）的显著下调和一些细胞周期调节基因（如 CDKN2A、CCNA2 等）的上调与乳腺癌的 MDR 密切相关。耐药癌细胞根据药物治疗表现出不同的基因表达模式，并且每种耐药表型可能在遗传上是不同的。需要进一步的功能研究来证明导致乳腺癌细胞耐药表型的完整基因集。
