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NVP-BEZ235 inhibits thyroid cancer growth by p53- dependent/independent p21 upregulation

Banjun Ruan1, Wei Liu1, Pu Chen1

  • 1Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, P.R. China.

International Journal of Biological Sciences
|February 7, 2020
PubMed

Insights

NVP-BEZ235 shows antitumor effects in thyroid cancer, even with p53 mutations. This dual PI3K/mTOR inhibitor

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • NVP-BEZ235 is a dual PI3K/mTOR inhibitor with demonstrated efficacy in various cancers.
  • Mutant p53 status often confers resistance to cancer therapies.
  • The effect of NVP-BEZ235 on thyroid cancer with different p53 statuses is not well understood.

Purpose of the Study:

  • To investigate the tumor-suppressing effects of NVP-BEZ235 in thyroid cancer cell lines and xenograft models with varying p53 statuses.
  • To elucidate the molecular mechanisms underlying NVP-BEZ235's efficacy, particularly in p53-mutant thyroid cancer.

Main Methods:

  • Utilized thyroid cancer cell lines and an in-vivo xenograft mouse model.
  • Examined the effects of NVP-BEZ235 on cell proliferation and cell cycle progression.
  • Analyzed p53-independent p21 upregulation and GSK3β/β-catenin signaling pathways.

Main Results:

  • NVP-BEZ235 demonstrated antitumor effects in both p53 wild-type and p53-mutant thyroid cancer cells, although effects were less pronounced in mutant cells.
  • p53-independent upregulation of p21 was identified as a key factor in the response of p53-mutant cells to NVP-BEZ235.
  • NVP-BEZ235 induced G0/G1 cell cycle arrest via p21-mediated inhibition of GSK3β/β-catenin signaling in both p53 wild-type and mutant thyroid cancer cells.

Conclusions:

  • NVP-BEZ235 exhibits therapeutic potential in thyroid cancer, irrespective of p53 mutation status.
  • p21 upregulation and GSK3β/β-catenin pathway inhibition are critical mechanisms mediating NVP-BEZ235's anti-cancer effects in thyroid cancer.
  • These findings suggest NVP-BEZ235 as a promising agent for thyroid cancer treatment, warranting further clinical investigation.
Keywords:
Cell cycle arrestNVP-BEZ235PI3K/Akt/mTORThyroid cancerp21p53

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