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Objective: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.Methods: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.Results: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.Conclusion: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.
Objective: 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. Methods: 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. DNA microarray containing 458 apoptosis-related human genes was used to compare the gene expression profiles GBC-SD / ATO cells and corresponding sensitive cell line GBC-SD. Results: 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 with> 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. Confluence: 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.