Drug resistance induced by paclitaxel and carboplatin plasmatic concentrations in lung cancer cell lines

97 Background: Multidrug resistance (MDR) phenotype is the major cause of chemotherapy failure. It has been related to several proteins expression: P-glycoprotein (PgP), MRP family, LRP, and BCRP. We study the resistance pattern induced after paclitaxel and carboplatin in non-small cell lung cancer (NSCLC). Methods: We used 5 different cell lines. A549 and A427 cell lines were derived from lung epithelial carcinoma. NODO line was obtained from lung carcinoma metastases, and 3 cell lines derived from other tumours: gastric cancer (GAS), seminoma (SEM), breast cancer (MCF7). The cell lines were exposed to paclitaxel, carboplatin, and the combination of both drugs. The concentrations we used were similar to the plasma concentrations observed in patients treated previously. Results: A549 cell line did not show basal expression of MDR1, but a weak basal expression of MRP3 was observed. After chemotherapy, we observed that paclitaxel induced MDR1 and carboplatin induced MRP3. The combination of both drugs induced MDR1 and MRP3 expression, however, when paclitaxel is associated to carboplatin, MRP3 expression did not increase significantly. A427 cell line did not show basal expression of MDR1 and MRP3. Paclitaxel induced MDR1 and carboplatin induced MRP3. The association of both drugs increased significantly the expression of MDR1, and very few the expression of MRP3. NODO cell line did not show any basal expression. Paclitaxel induced MDR1 and carboplatin induced MRP3. Cell lines derived from other tumours not show any basal expression. Paclitaxel induced MDR1 in all cell lines. Carboplatin did not induce MDR1, nor MRP3 in GAS cell line. Conclusions: Plasma concentrations of paclitaxel induced MDR1 expression but not MRP3 in lung cancer and other tumours derived cell lines. Carboplatin produced overexpression of MRP3 but not MDR1 in the same cell lines. The combination of both drugs at plasma concentrations was not able to activate a new resistance mechanism in the studied cell lines, but improve the resistance mechanism induced by each one of the drugs individually.