Type 2 diabetes mellitus promotes the proliferation, metastasis, and suppresses the apoptosis in oral squamous cell carcinoma

Background: Our previous study revealed that patients with oral squamous cell carcinoma and concomitant type 2 diabetes mellitus presented a lower 5-year survival rate. Hyperglycemia has been increasingly recognized as a risk factor for more advanced disease and poorer prognosis in patients with oral squamous cell carcinoma. However, its role remains unclear.

Methods: The expressions of BRIP1, Ki67, E-cadherin, and cleaved caspase-3 were detected by immunohistochemistry in oral squamous cell carcinoma tissues with or without type 2 diabetes mellitus. Cell counting kit-8 assay and wound healing assay were used to determine the proliferative and migratory ability of oral squamous cell carcinoma cells cultured with or without high glucose in vitro. Flow cytometry was applied to distinguish the role of high glucose on the cell cycle and apoptosis rates.

Results: The expression level of Ki67 was elevated while BRIP1, E-cadherin, and cleaved caspase-3 were downregulated in patients with oral squamous cell carcinoma coexisting with diabetes. The cell proliferation and migration in oral squamous cell carcinoma cell lines were significantly enhanced by high glucose. Flow cytometric analysis suggested that high glucose predisposed cancer cells to stay at S/G₂ phase and to exhibit lower apoptosis rates.

Conclusion: Our results implicated that type 2 diabetes mellitus may play a crucial role in the development and progression of oral squamous cell carcinoma through hyperglycemia, affecting cancer cell proliferation, migration, and apoptosis. This finding might provide a new direction for the prevention and treatment of oral squamous cell carcinoma.