Experimental Exploration for Genes Related to Susceptibility and Resistance to Irinotecan

Anticancer Res. 2022 Aug;42(8):4011-4016. doi: 10.21873/anticanres.15897.

Abstract

Background/aim: Anticancer drug resistance is an important issue in cancer treatment. Multiple genes are thought to be involved in resistance to anticancer drugs; however, this is still not fully understood. This study aimed to identify the genes involved in irinotecan resistance and their functional characteristics.

Materials and methods: Gene trap insertion mutant Chinese hamster ovary (CHO) cells were used in the experiments, and next-generation sequencing, gene-ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to evaluate the biological functions of differentially expressed genes (DEGs).

Results: In total, 2,134 DEGs were identified, including 1,216 up-regulated and 918 down-regulated genes. In KEGG pathways, microRNAs in cancer were significantly associated with up-regulated DEGs, while spliceosome and p53 signaling pathways were significantly associated with down-regulated DEGs. The pathway analysis identified several genes that might be involved in irinotecan resistance.

Conclusion: Using CHO cells, the genes involved in irinotecan resistance and functional characteristics were predicted. These results provide new clues for predicting irinotecan resistance.

Keywords: Chinese hamster ovary cell; cancer; chemotherapy; drug resistance; genetic mutation; irinotecan.

MeSH terms

  • Animals
  • CHO Cells
  • Computational Biology* / methods
  • Cricetinae
  • Cricetulus
  • Gene Expression Profiling* / methods
  • Gene Ontology
  • Humans
  • Irinotecan / pharmacology

Substances

  • Irinotecan