二甲双胍通过调控STAT3的表达抑制头颈部肿瘤转移机制的研究

Metformin Inhibits the Metastasis of Head and Neck Cancer by Regulating the Expression of STAT3

探讨二甲双胍是否通过调控STAT3的表达抑制头颈部肿瘤的EMT和迁移.在头颈部肿瘤686LN细胞株上给予二甲双胍处理,Western blot检测上皮-间叶样转化(EMT)相关蛋白的表达;通过Transwell实验检测二甲双胍对头颈部肿瘤细胞迁移能力的影响;在高转移特性的头颈部肿瘤细胞株和配对的低转移特性的细胞株上,检测STAT3蛋白表达;用脂质体转染STAT3的小干扰RNA,检测头颈部肿瘤EMT相关蛋白的表达;在686LN上给予IL-6处理或者给予二甲双胍处理或者同时给予IL-6和二甲双胍处理,检测STAT3蛋白和EMT相关蛋白表达;以及通过Transwell实验检测二甲双胍对IL-6诱导的细胞迁移的影响.结果显示,给予二甲双胍处理,抑制头颈部肿瘤的EMT,并且细胞迁移能力减弱. STAT3磷酸化和总蛋白在高转移特性的头颈部肿瘤细胞株高表达.转染STAT3 siRNA抑制STAT3的表达可抑制头颈部肿瘤的EMT.二甲双胍抑制IL-6介导的STAT3磷酸化水平升高,抑制IL-6诱导的EMT,同时二甲双胍抑制IL-6诱导的细胞迁移.结论说明,二甲双胍抑制头颈部肿瘤EMT和细胞迁移,并且能抑制IL-6介导的STAT3磷酸化水平升高,其抑制头颈部肿瘤迁移作用机制可能与下调STAT3的磷酸化水平有关.

To study whether metformin can inhibit the epithelial-mesenchymal transition and migration of head and neck cancer by regulating the expression of STAT3. Metformin was given on the head and neck cancer 686LN cell line and Western blot was used to detect related protein of epithelial-mesenchymal transition(EMT). The effect of metformin on head and neck cancer cell migration was determined by transwell assay. Western blot anlaysis was used to detect the expression of STAT3 in a highly metastatic head and neck cancer cell line and a paired low metastatic cell line. STAT3 siRNA transfected in head and neck cancer to detect the effect of STAT3 on EMT. Western blot anlaysis was used to detect the expression of STAT3 and EMT related protein in 686LN cells treated with IL-6 or metformin. The effect of metformin on cell migration induced by IL-6 by transwell assay. The EMT and the cell migration ability were inhibited in 686LN cells treated with metformin. The expressin of STAT3 phosphorylation and total protein in high level in the highly metastatic head and neck cancer cell line. Transfection of STAT3 siRNA inhibited the expression of STAT3 could inhibit the EMT of head and neck cancer. Metformin inhibited IL-6 mediated STAT3 phosphorylation and inhibits IL-6 induced EMT,while metformin inhibited IL-6 induced cell migration. The results showed that,metformin inhibited EMT and cell migration,and can inhibit IL-6 mediated STAT3 phosphorylation in head and neck cancer,which inhibited the metastasis of head and neck cancer may be related to the downregulation of the phosphorylation level of STAT3.