The role of CIP2A as a therapeutic target of rapamycin in radioresistant head and neck cancer with TP53 mutation

Head Neck. 2019 Sep;41(9):3362-3371. doi: 10.1002/hed.25868. Epub 2019 Jul 3.

Abstract

Background: CIP2A may activate multiple oncogenic proteins and promote the proliferation of various cancer cells.

Methods: We investigated that the role of CIP2A in radioresistant head and neck cancer (HNC) cell line with TP53 mutation and the effect of the rapamycin on the response of HN31 with TP53 mutation cells to irradiation related to CIP2A expression.

Results: CIP2A expression was stimulated by p53 mutation and critical for the inhibition of senescence induction in response to radiation. The treatment with radiation alone neither induced cytotoxicity in HN31 cells nor completely suppressed the activation of CIP2A. However, the combination of radiation and rapamycin increase the radiosensitivity through the induction of senescence with downregulation of CIP2A expression both in vivo and in vitro.

Conclusion: Our results suggest that CIP2A may serve as a therapeutic target of rapamycin through induction of senescence in radioresistant HNC with TP53 mutation.

Keywords: CIP2A; TP53 mutation; head and neck cancer; radioresistance; rapamycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Autoantigens / metabolism*
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Proteins / metabolism*
  • Mice
  • Mutation / genetics
  • Neoplasm Transplantation
  • Radiation Tolerance
  • Sirolimus / pharmacology*
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antibiotics, Antineoplastic
  • Autoantigens
  • CIP2A protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Sirolimus