Regulation and role of nuclear factor-E2-related factor 2 (Nrf2) in multidrug resistance of hepatocellular carcinoma

Chem Biol Interact. 2018 Jan 25:280:70-76. doi: 10.1016/j.cbi.2017.12.014. Epub 2017 Dec 6.

Abstract

Hepatocellular carcinoma (HCC) chemoresistance, which is regarded as a kind of stress management reaction to chemotherapy drugs, severely hinders the therapy outcomes of HCC treatment. Stress management is generally achieved by activating certain signal pathways and chemical factors, among which, nuclear factor-E2-related factor2 (Nrf2) is a key factor in HCC chemoresistance formation. Nrf2 is a nuclear factor that coordinates the induction and expression of a battery of genes encoding cytoprotective proteins when participating in the Nrf2antioxidant response element (Nrf2/ARE) pathway, which is one of the most important intracellular antioxidant stress pathways. This review summarizes the recent understanding of the involvement of Nrf2 in the chemoresistance of liver cancer, its target proteins, expression regulation and potential Nrf2 inhibitors that sensitize chemotherapy drugs in HCC.

Keywords: Chemoresistance; HCC; Nrf2; Regulation; Sensitivity.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cullin Proteins / metabolism
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Signal Transduction / drug effects

Substances

  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • CUL3 protein, human
  • Cullin Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2