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2 型糖尿病促进口腔鳞状细胞癌的增殖、转移,并抑制其凋亡。

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

机构信息

Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya hospital of Central South University, Changsha, Hunan, China.

Research Center of Oral and Maxillofacial Tumor, Xiangya hospital of Central South University, Changsha, Hunan, China.

出版信息

J Oral Pathol Med. 2022 May;51(5):483-492. doi: 10.1111/jop.13244. Epub 2021 Oct 1.

DOI:10.1111/jop.13244
PMID:34551155
Abstract

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 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.

摘要

背景

我们之前的研究表明,患有口腔鳞状细胞癌和 2 型糖尿病的患者的 5 年生存率较低。高血糖已被越来越多地认为是口腔鳞状细胞癌患者疾病进展和预后较差的危险因素。然而,其作用仍不清楚。

方法

采用免疫组织化学法检测伴有或不伴有 2 型糖尿病的口腔鳞状细胞癌组织中 BRIP1、Ki67、E-钙黏蛋白和 cleaved caspase-3 的表达。细胞计数试剂盒-8 测定法和划痕愈合试验用于测定体外高糖培养的口腔鳞状细胞癌细胞的增殖和迁移能力。流式细胞术用于区分高糖对细胞周期和细胞凋亡率的作用。

结果

患有合并糖尿病的口腔鳞状细胞癌患者的 Ki67 表达水平升高,而 BRIP1、E-钙黏蛋白和 cleaved caspase-3 的表达水平降低。高葡萄糖显著增强了口腔鳞状细胞癌细胞系的细胞增殖和迁移能力。流式细胞术分析表明,高葡萄糖使癌细胞更容易停留在 S/G 期,并表现出较低的细胞凋亡率。

结论

我们的研究结果表明,2 型糖尿病可能通过高血糖在口腔鳞状细胞癌的发生和发展中发挥关键作用,影响癌细胞的增殖、迁移和凋亡。这一发现可能为口腔鳞状细胞癌的预防和治疗提供新的方向。

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