Relationship Between Epithelial-mesenchymal Transition Induced By Hypoxia And Invasive Ability In Hepatocellular Carcinoma Cells

Objective: To study whether epithelial-mesenchymal transition (EMT) is iduced by hypoxia and promotes the migratory and invasive ability in hepatocellular carcinoma cells, which may provide us a new idea on therapy of hepatocellular carcinoma.Method: We chose two hepatocellular carcinoma cell lines with different metastatic ablity and established the hepatocellular carcinoma cell culture system with 5% CO2 and 95% N2, simulating the circumstance of hypoxia. Then we observed the shape changes of the cells by inverted microscope, evaluated the expression of epithelial specific protein such as E-Cadherin and mesenchymal specific protein such as Vimentin by Western-blot and analyzed the gradation value and relative magnitude with image analysis software. We also analyzed the migratory and invasive ability of hepatocellular carcinoma cell by Transwell chamber migratory and invasive culture system.Result: The hepatocellular carcinoma cells cultured under hypoxic system were transformed from epithelial and tighten state to spindle and unconsolidated state, observed under inverted microscope, loosing intercellular junction. Western-blot showed that the expression of epithelial specific protein E-Cadherin was significantly lower (P<0.01) and the expression of mesenchymal specific protein Vimentin was significantly higher (P<0.01) than the one cultured under normoxic system. Transwell chamber cell culture system indicated that the migratory and invasive ability of hepatocellular carcinoma cells was significantly enhanced under hypoxic system (P<0.01). Compared two hepatocellular carcinoma cell lines, we found that the changes of cell lines with higher metastatic ablity were more obvious than the lower ones. Conclusion: Hypoxia causes epithelial-mesenchymal transition, enhances the ability of migration and invasion in hepatocellular carcinoma cells and further leads to distant metastasis. And the hepatocellular carcinoma cells with higher metastatic ablity are obviously influenced by hypoxia.