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Metformin inhibits cell proliferation and ACTH secretion in AtT20 cells via regulating the MAPK pathway

Yingxuan Sun1, Jianhua Cheng1, Ding Nie1

  • 1Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Molecular and Cellular Endocrinology
|December 26, 2023
PubMed

Insights

Metformin effectively inhibits pituitary tumor growth and adrenocorticotropic hormone (ACTH) secretion by suppressing the MAPK pathway. This suggests metformin as a potential treatment for Cushing's disease.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Pituitary corticotroph tumors cause excess ACTH secretion, leading to Cushing's disease.
  • Current treatments for Cushing's disease have limitations, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the effects of metformin on ACTH secretion and pituitary tumor progression.
  • To elucidate the molecular mechanisms underlying metformin's action, focusing on the MAPK pathway.

Main Methods:

  • In vitro studies using AtT20 cells treated with metformin, assessing cell viability, ACTH secretion, cell cycle, and protein expression.
  • RNA sequencing to identify differentially expressed genes and pathways.
  • In vivo xenograft models in nude mice to evaluate metformin's effect on tumor growth and ACTH levels.

Main Results:

  • Metformin inhibited AtT20 cell proliferation, decreased ACTH secretion, and induced G1/S phase arrest.
  • RNA sequencing identified MAPK pathway involvement, with decreased phosphorylation of ERK1/2 and JNK observed.
  • Combined treatment with metformin and an ERK1/2 inhibitor showed enhanced inhibition of proliferation and POMC expression.
  • In vivo studies confirmed metformin's suppression of tumor growth and ACTH secretion.

Conclusions:

  • Metformin demonstrates potential as a therapeutic agent for pituitary corticotroph tumors and Cushing's disease.
  • The drug's efficacy may be mediated through the suppression of the MAPK signaling pathway.
  • Further clinical investigation of metformin for Cushing's disease is warranted.
Keywords:
MAPK pathwayMetforminPituitary corticotroph tumorsUlixertinib

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