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

Wei-Ming Wang,Shu-Hui Shao,Huan-Quan Nie,Si-Si Yang,Jing Zhang,Tong Su

doi:10.3389/fendo.2022.828608

Abstract

PurposeType 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.MethodsThis 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.ResultsEGFR 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.ConclusionMetformin 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.

Highlights

Oral squamous cell carcinoma (OSCC) is one of the main malignant tumors of the head and neck, accounting for approximately 90% of all oral malignancies [1]
29 patients with OSCC and Type 2 diabetes mellitus (T2DM) were taking metformin, and 54 patients were treated with other methods of hypoglycemic treatment
Our results show that in OSCC patients with T2DM, the expression level of epidermal growth factor receptor (EGFR) has no correlation with blood glucose levels, but after excluding the factor of taking metformin, the expression of EGFR is positively correlated with FBG fluctuations

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is one of the main malignant tumors of the head and neck, accounting for approximately 90% of all oral malignancies [1]. It is a huge health problem facing the world, and its statistics has hardly changed over time [2]. Type 2 diabetes mellitus (T2DM) is an emerging systemic factor in the occurrence of OSCC [4, 5]. Hyperglycemia is one of the most important factors that promote tumor transformation of potential oral malignant diseases [9, 10]. Hyperglycemia stimulates cell proliferation, growth factor signaling, and chemoresistance in various cancer types [4, 5, 10]

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Conclusion