The Expression of Connexin 26 Regulates the Radiosensitivity of Hepatocellular Carcinoma Cells through a Mitogen-Activated Protein Kinases Signal Pathway

Int J Mol Sci. 2022 Nov 24;23(23):14644. doi: 10.3390/ijms232314644.

Abstract

Connexin 26 (Cx26) is a protein that constitutes a gap junction and is widely expressed in the liver. Abnormal expression of Cx26 is one of the important mechanisms of liver cancer, and is closely related to the transmission of radiation damage signals between cells. In the present study, we investigated the radiosensitivity of hepatocellular carcinoma (HCC) cells HepG2, with low expression of Cx26, and SK-hep-1, with high expression of Cx26 after X-ray irradiation. The cell survival, micronucleus formation and protein expressions of the mitogen-activated protein kinases (MAPK) signaling pathway were detected. The expression level of Cx26 could affect the radiosensitivity of liver cancer cells by affecting the phosphorylation of p38 and ERK proteins and regulating the expression of downstream NF-κB. Cell lines with knock-out and overexpression of Cx26 were also built to confirm the findings. Our results suggested that Cx26 might play an important role in the radiosensitivity of liver cancer and could be a potential target for clinical radiotherapy of liver cancer.

Keywords: MAPK; NF-κB; connexin 26; hepatocellular carcinoma; radiosensitivity.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / radiotherapy
  • Cell Line
  • Cell Line, Tumor
  • Connexin 26* / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / radiotherapy
  • Mitogen-Activated Protein Kinases / metabolism
  • Radiation Tolerance
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Connexin 26
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • GJB2 protein, human