Identification Of Genes Associated With 5-fluorouracil Resistance In Human Pancreatic Cancer Cells

Background & Aims: Using gene expression data, we compared the expression profile of 5-fluorouracil (5-FU) resistance in pancreatic cancer cells after in vitro selection low- and high-resistance phenotypes. The aims of our study were to identify genes showing altered expression in resistant derivatives, as well as several central genes or important pathways that were associated with 5-FU resistance in pancreatic cancer cells.Methods: The 5-FU-resistant MIAPaCa-2 derivatives were developed through exposure to increasing concentrations of 5-FU with repeated subcultures until the cells became fully resistant to 5-FU. Gene array analysis of the 5-FU-resistant MIAPaCa-2 derivatives and the parent cell line was performed using a Uniset Human 20K I Codelink Bioarray. Data were analyzed with CodeLink System Software. The expression profiling of selected genes were confirmed by real-time PCR assays. Results: We got successively two resistant derivatives, the low-resistance phenotype MIA-FU-2.4 and the high-resistance phenotype MIA-FU-10.0, These two derivatives can grow stably in 2.4μg/ml and 10.0μg/ml of 5-FU concentration respectively. Analysis of array data showed that the resistance of 5-FU in pancreatic cancer cell involved in widespread transcriptional activation. In MIA-FU-2.4 and MIA-FU-10.0, we identified respectively 1075 and 1628 differentially expressed genes. The biological functions of these genes included cell cycle, cell adhesion, signal transduction, DNA repair and apoptosis et al.Conclusions: Our data suggest that 5-FU resistance development in pancreatic cancer cell MIAPaCa-2 involves in many aspects of the biological functions and might be mainly attributed to apoptosis, DNA repair and cell cycle mechanisms and some signal transductions or some pivotal genes.