细胞自噬在头颈部鳞状细胞癌侵袭转移中的作用

The role of autophagy in the invasion and metastasis of the squamous cell carcinoma of head and neck

目的:探讨自噬在TGF-β1调控EMT诱导头颈鳞癌侵袭转移中的作用。方法:不同浓度及时间点TGF-β1构建头颈鳞癌上皮-间质转化(EMT)模型,Western blot检测自噬相关蛋白LC3水平;自噬抑制剂氯喹(CQ)抑制自噬后,Western blot检测上皮细胞标志物钙黏蛋白、间质细胞标志物波形蛋白及LC3蛋白的表达;划痕、Transwell侵袭小室实验检测自噬对头颈鳞癌侵袭、转移的影响。结果:不同浓度及时间点TGF-β1诱导EMT的同时,诱导发生自噬,且随着TGF-β1浓度的增加及时间的延长,自噬随之增强;自噬被抑制后,E-cadherin表达上调、Vimentin表达下调,细胞迁移及侵袭潜能较对照组明显减弱。结论:TGF-β1诱导头颈鳞癌发生EMT的同时伴随自噬;自噬在TGF-β1调控头颈鳞癌EMT的过程中,能增强其侵袭、转移能力。

Objective： The aim of this study is to explore the effects of autophagy on the metastasis of the Squamous Cell Carcinoma of Head and Neck（SCCHN） via epithelial to mesenchymal transition（EMT） induced by TGF-β1. Method： Establish the EMT model induced by TGF-β1 in the SCCHN in time/concentration, and the ex- pression of autophagy related protein microtubule associated protein 1 light chain3（LC3） detected by western blot; Autophagy inhibitor chloroquine （CQ）, depressing autophagy, the expression of E-cadherin, cytokeratin, Vimen- tin and LC3 were examined by Western blot. Wound healing and Transwell invasion assay indicate the effects to metastasis for SCCHN. Result： Autophagy was activated within TGF-β1 induced EMT model in the SCCHN in time/concentration dependently. After autophagy was suppressed, the expression of E-cadherin and cytokeratin increased while vimentin and the capacity of metastasis was reduced compared with control group. Conclusion： TGF-β1 induce EMT and Autophagy in the SCCHN. Autophagy could enhances metastasis in the SCCHN via EMT induced by TGF-β1.