Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma

Front Endocrinol (Lausanne). 2022 Feb 9:13:828608. doi: 10.3389/fendo.2022.828608. eCollection 2022.

Abstract

Purpose: Type 2 diabetes mellitus (T2DM) is among the risk factors for the occurrence and development of cancer. Metformin is a potential anticancer drug. Epidermal growth factor receptor (EGFR) plays an important role in the progression of oral squamous cell carcinoma(OSCC), but the relationship between metformin and EGFR expression in OSCC remains unclear.

Methods: This study involved the immunohistochemical detection of EGFR expression in cancer tissues of patients with T2DM and OSCC. The patients were divided into groups according to whether they were taking metformin for the treatment of T2DM, and the expression of EGFR in different groups was compared. Correlation analysis between the expression of EGFR and the fluctuation value of fasting blood glucose (FBG) was carried out. Immunohistochemistry was used to detect the expression of EGFR in cancer tissues of patients with recurrent OSCC. These patients had normal blood glucose and took metformin for a long time after the first operation.

Results: EGFR expression in T2DM patients with OSCC taking metformin was significantly lower than that in the non-metformin group. FBG fluctuations were positively correlated with the expression of EGFR in the OSCC tissues of the non-metformin group of T2DM patients. In patients with recurrent OSCC with normal blood glucose, metformin remarkably reduced the expression of EGFR in recurrent OSCC tissues.

Conclusion: Metformin may regulate the expression of EGFR in a way that does not rely on lowering blood glucose. These results may provide further evidence for metformin in the treatment of OSCC.

Keywords: EGFR; OSCC; blood glucose; metformin; type 2 diabetes mellitus.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Immunohistochemistry
  • Male
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Middle Aged
  • Mouth Neoplasms / complications
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / complications
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / metabolism*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Metformin
  • EGFR protein, human
  • ErbB Receptors