Determination of mechanisms of multiple drug resistance in MCF-7 cell line developed against paclitaxel and vincristine by microarray analysis

OBJECTIVES Acquired or intrinsic multiple drug resistance (MDR) is one of the limitations for successful chemotherapy. In this study, MDR mechanisms developed after paclitaxel and vincristine application in MCF-7 cell line were investigated. METHODS Paclitaxel and vincristine were applied to MCF-7 cell line in stepwise manner. The resistance levels of the cells were determined by XTT test. The levels of all of the genes in resistant and sensitive cells were determined by microarray assay. RESULTS MCF-7/400nMPac and MCF-7/120nMVinc cells are 150- and 30-fold resistant compared to sensitive MCF-7. Upregulation of MDR1 gene is found to be important in resistance. The expression levels of the genes encoding detoxifying enzymes were upregulated and some apoptotic gene levels were downregulated. Changes in expression levels of metastatic genes, some oncogenes, cell cycle, and tubulin-related genes were found. CONCLUSION According to these results, change in expression level of MDR1 gene seems to be important in resistance in MCF-7 cells.