Reversal of paclitaxel resistance in MCF-7 cell line by achemical modulator elacridar

Şener, Emine Çiğdem
The phenomenon called multi drug resistance (MDR) is the resistance of cancer cells to anticancer drugs before or during chemotherapy. One of the mechanisms causing MDR is the upregulation of efflux pumps. The overexpression of MDR1 and MRP1 results in increased efflux of anticancer agents. The aim of this study was to reverse MDR1-mediated paclitaxel resistance in MCF7 breast cancer cell line by a chemical MDR modulator elacridar. In this study, cytotoxicity and the reversal effect of elacridar on sensitive and paclitaxel resistant cells were investigated. The effect of elacridar on MDR1 and MRP1 gene expressions were also determined. Results indicated MDR1 gene was highly overexpressed (208 fold) in MCF7/Pac cells compared to MCF7/S cells. Elacridar was not found to be cytotoxic in MCF7/Pac cells up to 30µM. XTT results demonstrated 0.5µM elacridar concentration was able to restore the antiproliferative effect of paclitaxel by 94% in MCF7/Pac cells. Complete MDR reversal was achieved at 5µM elacridar concentration. qPCR results revealed dose dependent upregulations in MDR1 and MRP1 gene expression levels after elacridar treatment which did not prevent reversal of MDR by elacridar. Elacridar was shown to be very effective against paclitaxel resistance in MCF7/Pac cells at low concentrations. Therefore, it can be a suitable candidate for therapeutic applications in patients who developed paclitaxel resistance. Nevertheless, dose dependent upregulations in MDR1 and MRP1 gene expressions should be taken into consideration and overdose elacridar administration should be avoided.