The Study Of HIF1? Regulating Hypoxia-induced Epithelial-mesenchymal Transition In GC And Related Mechanisms

Background and objective:Gastric carcinoma (GC) is a major cause of death induced by malignant tumors. Various treatment and technology have made considerable progress, but its prognosis remains poor, and keeps a high mortality rate. Even underwent radical surgery, postoperative recurrence rate is still as high as 40-80%, 5-year survival rate of patients with gastric cancer is 20-30%. Tumor recurrence, metastasis and resistance to chemotherapy are responsible for the poor prognosis. Hypoxia can induce tumor metastasis and resistance to chemotherapy. In this process, epithelial-mesenchymal transition(EMT) is considered to be the initial part. This paper aims to study the regulation of hypoxia to EMT in gastric cancer and its related mechanisms.Methods:Choose the gastric cancer cell lines AGS and SGC7901, culture them under hypoxic condition for 48 hours, detect the expression levels of hypoxia inducible factor 1? (HIF1?). Then, choose AGS cell line, under normoxic condition, Lv-HIF1?/Si-HIF1? under normoxic condition, hypoxic condition, Lv-HIF1?/Si-HIF1? under hypoxic condition, EMT related biomarkers were investigated, such as E-cadherin, Vimentin(VIM), ZEB1, Snail and matrix metalloproteinase-2(MMP-2). Transwell experiment was used to validate changes of invasion and metastasis ability among the above conditions. Finally, under hypoxic conditions, western blot test was adopted to detect the expression of HIFla after the addition of PI3K/Akt inhibitors, and Transwell experiment to observe the invasion and metastasis ability.Results:Under hypoxia, HIF1? protein levels were elevated in both cell lines. In AGS cell line, both hypoxia and increasing of HIF1? made the expression of protein E-cadherin decreased and VIM increased. Simultaneously, the secretion of MMP-2 and expression of transcription factors ZEB1 and Snail were increased, and the invasion and migration capacity were enhanced. Knocking down HIF1? under hypoxic conditions, we got the contrary results to the above. Under hypoxia, after PI3K/Akt inhibitors were added, expression of HIFla decreased, and capacity of invasion and migration weakened.Conclusion:Under hypoxia, expression of HIF1? increased in gastric cancer cells, with EMT and ability of migration and invasion enhancing. These results can be reversed after Si-HIF1?. This procedure maybe involved in PI3K/Akt pathway.