Mechanism of drug resistance identified in human lung adenocarcinoma cell line SPC-A1 selected for resistance to docetaxel

Abstract

To investigate the mechanism of resistance to docetaxel in human lung cancer. Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vitro. The cDNA microarray identified a set of differentially expressed genes, and some genes were confirmed by RT-PCR. P-glycoprotein level was measured by flow cytometry analysis. The results of drug sensitivity measured by MTT assay showed that SPC-A1/Docetaxel cells were 13.2-fold resistant to docetaxel and cross-resistant at varying levels to other drugs. The cDNA microarray results identified a set of differentially expressed genes, which showed 428 genes that were up-regulated and 506 genes that were down-regulated in SPC-A1/Docetaxel cells, and some genes were confirmed by RT-PCR. Flow cytometry analysis suggests expression of P-glycoprotein (P-gp) was more abundant in SPC-A1/Docetaxel cells than in the parental cells and docetaxel selection reduces the apoptotic response. The results suggest that docetaxel selection led to changes in gene expression that contribute to the multidrug resistance phenotype.