CUL4B increases platinum-based drug resistance in colorectal cancer through EMT: A study in its mechanism

J Cell Mol Med. 2022 Dec;26(23):5767-5778. doi: 10.1111/jcmm.17585. Epub 2022 Nov 16.

Abstract

Platinum-based chemotherapy drugs play a very important role in the treatment of patients with advanced colorectal cancer, but the drug resistance of platinum-based chemotherapy drugs is an important topic that puzzles us. If we can find mechanisms of resistance, it will be revolutionary for us. We analysed the differential genes, core genes and their enrichment pathways in platinum-resistant and non-resistant patients through a public database. Platinum-resistant cell lines were cultured in vitro for in vitro colony and Transwell analysis. Tumorigenesis analysis of nude mice in vivo. Verify the function of core genes. Through differential gene and enrichment analysis, we found that CUL4B was the main factor affecting platinum drug resistance and EMT. Our hypothesis was further verified by in vitro drug-resistant and wild-type cell lines and in vivo tumorigenesis analysis of nude mice. CUL4B leads to platinum drug resistance in colorectal cancer by affecting tumour EMT.

Keywords: CUL4B; EMT; colorectal cancer; drug resistance.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis
  • Cell Transformation, Neoplastic
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Drug Resistance / genetics
  • Drug Resistance, Neoplasm* / genetics
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Mice
  • Mice, Nude
  • Platinum Compounds* / pharmacology
  • Platinum Compounds* / therapeutic use

Substances

  • Antineoplastic Agents
  • Platinum Compounds