The Study Of Hypoxia-induced EMT In HCC And Its Mechanisms

Purpose:Primary hepatocellular carcinoma(HCC) is one of the most common and high mortality carcinoma in China. About 50% of the world’s liver cancer patients are in china. Hypoxia is a common phenomenon in many solid tumors. Tumor cells can produce a series of adaptive changes in hypoxic conditions so as to promote the proliferation, migration and invasion function. Epithelial mesenchymal transition is an important step in tumor invasion and metastasis, we intend to study the hypoxic conditions in HCC epithelial mesenchymal transition and preliminary explore its mechanism.Methods:We choose HepG2, SMMC7721 two cell lines and establish hypoxia model. Observe changes of cell phenotypes under hypoxic condition. Detect the expression of hypoxia inducible factor HIF-1 alpha in Oh,24h,48h,72h. Protein levels were detected in EMT related biomarkers:cell surface protein E-cadherin, N-cadherin of cytoskeleton, transcription factor Twist, Snail. Detect the expression of TGF-β1 signaling pathway related proteins:TGF-β1, SMAD2, p-SMAD2, SMAD3, p-SMAD3. Transwell migration and invasion of hepatocellular carcinoma cells in hypoxia experiment under the condition of the change of cell migration and invasion ability.Results:Under hypoxic conditions, connections between cells were loose, cells were spindle shaped and stretched out pseudopodia. In hypoxic Oh,24h,48h,72h protein levels of HIF-1 alpha increased monitoring. The cell surface expression of E-cadherin protein decreased gradually with the increase of hypoxia, cell surface protein N-cadherin, protein Vimentin, transcription factor Twist, Snail expression increased with the increase of hypoxia. The expression of TGF- beta signaling pathway related protein:TGF-beta 1, p-SMAD2, p-SMAD3 were increased with the increased time of hypoxia. Hepatocellular carcinoma cell invasion and migration ability were enhanced under hypoxic conditions compared with normoxia.Conclusion:The epithelial mesenchymal transition of liver cancer cells under hypoxia condition, reduce the epithelial cell markers, interstitial marker increased, and enhance the ability of invasion and metastasis. May be related to hypoxic conditions TGF- beta signaling pathway activation, transcription factor Twist, the increased expression of Snail related.