FGF21 promotes non-small cell lung cancer progression by SIRT1/PI3K/AKT signaling

Life Sci. 2021 Mar 15:269:118875. doi: 10.1016/j.lfs.2020.118875. Epub 2020 Dec 10.

Abstract

Aims: Lung cancer is a key contributor to the cancer-related death throughout the world. FGF21 (fibroblast growth factor 21) has been found to regulate various pulmonary diseases, whereas, the role and mechanism of FGF21 in lung cancer remain unclear. The aim of this research was to explore the expression and function of FGF21 in lung cancer.

Main methods: The mRNA and protein expression of FGF21 were analyzed through qRT-PCR and western blot, respectively. Cell proliferation, apoptosis and migration were analyzed by CCK-8 assay, flow cytometry and wound-healing assay, respectively. ROS, SOD, LDH and CK were examined with respective commercially kit.

Key findings: FGF21 level was increased in lung cancer tissue samples and cell lines at both mRNA and protein levels. Overexpressing FGF21 promoted cell growth and migration significantly. It also increased SOD and reduced ROS, LDH and CK contents. By contrast, down-regulated FGF21 presented the opposite effect on lung cancer cells. Furthermore, FGF21 may function as a tumor promotor by activating the SIRT1/PI3K/AKT signaling pathway in lung cancer.

Significance: This study demonstrated that FGF21 was a tumor promoter in lung cancer development, serving as a feasible therapeutic target in the treatment of lung cancer.

Keywords: Cell progression; FGF21; Lung cancer; SIRT1/PI3K/AKT signaling.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression*
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Oxidative Stress / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Sirtuin 1 / metabolism*
  • Up-Regulation / genetics

Substances

  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Proto-Oncogene Proteins c-akt
  • Sirtuin 1