Abstract:

Objective To investigate the effect and molecular mechanism of HIF-1α on migration and invasion of hepatocellular carcinoma（HCC） cells induced by hypoxia. Methods  Human normal hepatocyte line WRL68， HCC cell line HepG2 and SMMC7721 were cultured under hypoxia and normal culture conditions. Real time quantitative PCR （QPCR） and Western blotting were used to detect the expression of HIF-1α mRNA and protein. HepG2 cells were transfected with NC nonsense nucleic acid sequence （NC group）， siHIF-1α（HIF-1α group） and siIL-8 （IL-8 group）， respectively. Western blotting was used to detect the expression of HIF-1α， IL-8 and NF-κB protein. The changes of migration and invasion ability of HepG2 were detected by interfering with HIF-1α and IL-8. Results Under hypoxia， the levels of HIF-1α mRNA and protein in HepG2 and SMMC7721 cell lines were significantly higher than those in normal human hepatocytes. Compared with the control group and NC group， the expression of HIF-1 alpha protein in HIF-1 alpha group decreased significantly to 0.39±0.077 （P＜0.05）. Under hypoxia， the expression of IL-8 protein in HIF-1α group was 0.31±0.043，significantly lower than that in blank control group and NC group， and the difference was statistically significant （P＜0.05）. The number of HepG2 migrating and invading cells in NC group were 91.2±8.2 and 121.1±6.7 respectively， which were significantly higher than those in HIF-1α group （36.3±5.9 and 47.7±3.3），and the difference was statistically significant （P＜0.05）；which were significantly higher than those in IL-8 group （49.4±5.6 and 39.6±5.1），and the difference was statistically significant （P＜0.05）.Conclusion HIF-1α promotes the migration and invasion of hypoxia induced hepatocellular carcinoma cells through regulating IL-8 expression.

Key words: Hepatocellular carcinoma, HIF-1α, IL-8, Migration, Invasion