ClC-3 chloride channel protein induces G1 arrest in hepatocellular carcinoma Hep3B cells

Oncol Rep. 2018 Jul;40(1):472-478. doi: 10.3892/or.2018.6416. Epub 2018 May 3.

Abstract

ClC-3 is a type of chloride channel that has multiple functions in tumorigenesis and tumor growth, and can be blocked by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid). In the present study, we found that DIDS inhibited the proliferation of Hep3B hepatocellular carcinoma (HCC) cells in a concentration-dependent manner. More in-depth research demonstrated that DIDS downregulated the protein expression levels of cyclin D1 and cyclin E, which are key proteins of the G1 phase. Additionally, we found that ClC-3 siRNA transfection induced G1 arrest in the Hep3B cells, confirming that ClC-3 is involved in the DIDS-induced inhibition of Hep3B cells. Moreover, the level of α-fetoprotein (AFP), a negative prognostic indicator of HCC, was decreased after treatment with DIDS and ClC-3 siRNA. In conclusion, we demonstrated that ClC-3 can arrest the cell cycle at the G1 phase to inhibit cell proliferation, suggesting that ClC-3 has the potential to be a novel target for HCC therapy and potentially improve the prognosis of HCC patients.

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chloride Channels / genetics*
  • Cyclin D1 / genetics
  • Cyclin E / genetics
  • G1 Phase / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • RNA, Small Interfering
  • alpha-Fetoproteins / genetics

Substances

  • Chloride Channels
  • ClC-3 channel
  • Cyclin E
  • RNA, Small Interfering
  • alpha-Fetoproteins
  • Cyclin D1
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid