CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway

Int J Biol Sci. 2021 Aug 19;17(13):3608-3621. doi: 10.7150/ijbs.64003. eCollection 2021.

Abstract

Purpose: The incidence of hepatocellular carcinoma (HCC) is extremely high, and China accounts for approximately 50% of global liver cancer cases. Previous studies reported that CDC20 is involved in the occurrence and progression of a variety of malignant tumors. So, whether CDC20 will affect the development of HCC, we have conducted in-depth research on this. Methods: We selected Hep3B and HepG2 for cell culture, and performed siRNA transfection, lentiviral infection, western blot, MTS determination, cell cycle determination, apoptosis test, immunodeficiency test, clone survival test and subcutaneous parthenogenesis in nude mice. Results: Knockdown of CDC20 greatly enhanced the radiation efficacy on the growth retardation in HepG2, and protein level of CDC20 was decreased for the activation of P53 by radiation. Downregulation of CDC20 combined with radiation can inhibit proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of HCC cells was gradually reduced with radiation dose increased in P53 mutated Hep3B cells. After knocking down CDC20 in HCC, Bcl-2 was down-regulated and Bax expression increased. Down-regulation of CDC20 can inhibit further invasion by promoting the radiosensitivity of HCC. Conclusion: In this study, we found that that CDC20 was highly expressed in HCC and participated in radio resistance of HCC cells with P53 mutation Bcl-2/Bax via signaling pathway. This study is the first to present evidence that CDC20 may play a role in improving the efficacy of radiotherapy in HCC.

Keywords: Bcl-2/Bax pathway; CDC20; P53 mutant; hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / radiotherapy
  • Cdc20 Proteins / metabolism*
  • Genes, p53*
  • Hep G2 Cells
  • Humans
  • Immunotherapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / radiotherapy
  • Mice
  • Mice, Nude
  • Radiation Tolerance
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Cdc20 Proteins
  • Transcription Factors
  • bcl-2-Associated X Protein
  • CDC20 protein, human
  • RBCK1 protein, human
  • Ubiquitin-Protein Ligases