Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells

Pharmacology. 2018;102(3-4):161-168. doi: 10.1159/000491587. Epub 2018 Jul 26.

Abstract

The nucleotide excision repair protein excision repair cross-complementation group 1 (ERCC1) has been repeatedly shown to be involved in the sensitivity of cancer cells to platinum derivatives. In order to better understand this process, we transfected HCT-116 cells with a plasmid encoding ERCC1 and studied their in vitro and in vivo behaviour. No main differences were observed for sensitivity to platinum drugs, DNA repair capacity and clonogenicity in vitro. However, -ERCC1-transfected HCT-116 cells showed paradoxical behaviour in vivo with increased growth in mice treated with oxaliplatin as compared to untreated mice. The Trop2 protein was identified as being potentially involved in the underlying mechanism for these observations, as it was overexpressed in transfected cells. Our results suggest complex regulation of signalling in cancer cells exposed to cancer drugs.

Keywords: Cancer; Excision repair cross-complementation group 1; Oxaliplatin; Tumour growth.

MeSH terms

  • Animals
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / pathology
  • DNA Repair
  • DNA, Complementary / administration & dosage
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Female
  • Humans
  • Mice
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • Transfection
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • DNA, Complementary
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • TACSTD2 protein, human
  • Oxaliplatin
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin