Establishment of an arsenic-resistant human gallbladder carcinoma cell line and analysis of the differential expressions of genes associated with apoptosis

Abstract

The aim of the study was to establish an arsenic trioxide (ATO)-resistant cell line of human gallbladder carcinoma, GBC-SD/ATO, and to analyze the differential expressions of its apoptosis-associated genes, so as to investigate a correlation between ATO induced resistance of gallbladder carcinoma and expressions of apoptosis associated genes. The resistant cell line was obtained in vitro by culture of human gallbladder carcinoma cell line GBC-SD with increasingly stepwise concentrations of ATO. The sensitivities of GBC-SD cells and GBC-SD/ATO cells to ATO were determined by MTT assay respectively. cDNA microarray containing 458 apoptosis-related human genes was used to compare the gene expression profiles of GBC-SD/ATO cells and corresponding sensitive cell line GBC-SD. GBC-SD/ATO cell line was established successfully after 8 months of exposure to increasing concentrations of ATO. Compared with the parental cell line, GBC-SD/ATO was 13.6 times more resistant to ATO. Of the 458 apoptosis-related genes, 17 genes were detected having > 2-fold difference of expression between the GBC-SD/ATO and GBC-SD cells, with 6 genes up-regulated and 11 genes down-regulated in GBC-SD/ATO cells. The 17 genes involved in the apoptosis pathway might be relevant to the resistance of GBC-SD/ATO cells to ATO, suggesting that the modulation of expression of apoptosis-related genes may be a main mechanism of acquired resistance in GBC-SD/ATO.