Identifying clinically relevant drug resistance genes in drug-induced resistant cancer cell lines and post-chemotherapy tissues

Oncotarget. 2015 Dec 1;6(38):41216-27. doi: 10.18632/oncotarget.5649.

Abstract

Until recently, few molecular signatures of drug resistance identified in drug-induced resistant cancer cell models can be translated into clinical practice. Here, we defined differentially expressed genes (DEGs) between pre-chemotherapy colorectal cancer (CRC) tissue samples of non-responders and responders for 5-fluorouracil and oxaliplatin-based therapy as clinically relevant drug resistance genes (CRG5-FU/L-OHP). Taking CRG5-FU/L-OHP as reference, we evaluated the clinical relevance of several types of genes derived from HCT116 CRC cells with resistance to 5-fluorouracil and oxaliplatin, respectively. The results revealed that DEGs between parental and resistant cells, when both were treated with the corresponding drug for a certain time, were significantly consistent with the CRG5-FU/L-OHP as well as the DEGs between the post-chemotherapy CRC specimens of responders and non-responders. This study suggests a novel strategy to extract clinically relevant drug resistance genes from both drug-induced resistant cell models and post-chemotherapy cancer tissue specimens.

Keywords: 5-fluorouracil; colorectal cancer; drug treatment response; drug-induced resistant cancer cell lines; oxaliplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Drug Resistance, Neoplasm / genetics*
  • Fluorouracil / administration & dosage
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Irinotecan
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis / methods
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pilot Projects
  • Signal Transduction / genetics

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Fluorouracil
  • Camptothecin