Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes

Abstract

Acquired resistance to chemotherapeutic drugs in gallbladder cancer (GBC) results in therapy failure. This study is aimed to establish oxaliplatin (OXA)-resistant GBC cell lines and uncover their gene expression profiles. First, two OXA-resistant GBC cell lines (GBC-SD/OXA and SGC996/OXA) were established by gradually increasing the drug concentration, and the resistance index was 4–5. The two resistant cell lines showed slower proliferation and higher stemness, colony formation, and migration abilities. Epithelial mesenchymal transformation and increased levels of P-glycoprotein were also detected. Next RNA-sequence analysis identified 4,675 dysregulated genes (DGs) in resistant cells, and most of the 12 randomly selected DGs were verified to be consistent with the sequence results. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several DGs were involved in resistance- and phenotype-related pathways, of which the activations of PD-L1 and ERK1/2 were both verified in resistant cell lines. In conclusion, this study is the first to report the gene expression profile of OXA-resistant GBC cells and provides a useful database for target development.

Keywords

• oxaliplatin
• gallbladder cancer
• resistant cell lines
• csf2
• gene expression profile