Type 2 diabetes mellitus promotes the proliferation, metastasis, and suppresses the apoptosis in oral squamous cell carcinoma
Type 2 diabetes mellitus promotes the proliferation, metastasis, and suppresses the apoptosis in oral squamous cell carcinoma
复制标题
2型糖尿病促进口腔鳞状细胞癌增殖、转移并抑制细胞凋亡
DOI：
10.1111/jop.13244
复制
发表时间：
2021-10-01
影响因子：
3.3
通讯作者：
Su, Tong
中科院分区：
文献类型：
--
作者：
Hu, Xin;Wu, Jin;Su, Tong
背景我们先前的研究表明，口腔鳞状细胞癌和伴随的2型糖尿病患者的生存率较低。高血糖越来越被认为是口服鳞状细胞癌患者的晚期疾病和预后较差的危险因素。但是，它的作用尚不清楚。方法通过在口腔鳞状细胞癌组织中通过免疫组织化学检测BRIP1，KI67，E-钙粘着蛋白和裂解的caspase-3的表达。细胞计数KIT-8分析和伤口愈合测定法用于确定在有或没有高葡萄糖体外培养的口服鳞状细胞癌细胞的增殖和迁移能力。使用流式细胞仪来区分高葡萄糖在细胞周期和凋亡率中的作用。结果，在与糖尿病共存的口服鳞状细胞癌患者中，BRIP1，E-钙粘着蛋白和裂解的caspase-3的表达水平升高，而BRIP1，E-钙粘蛋白和裂解的caspase-3下调。高葡萄糖可显着增强口腔鳞状细胞癌细胞系中的细胞增殖和迁移。流式细胞仪分析表明，高葡萄糖易感性癌细胞保持在S/G（2）期，并表现出较低的凋亡率。结论我们的结果表明，2型糖尿病可能在口腔鳞状细胞癌通过高血糖的发展和进展中起关键作用，从而影响癌细胞的增殖，迁移和凋亡。这一发现可能为预防和治疗口服鳞状细胞癌提供了新的方向。
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/G(2) 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.