Expression Of HIF-1α、Twist In Gastirc Carcinoma And Their Relationship With Epithelial-mesenchymal Transition

Objective：To investigate the relationship between the expressions of Hif-1α, Twistand clinical pathological parameters in gastric carcinoma. Explore its significance injudging the prognosis of patients. Analyze the expression of two proteins in theepithelial-mesenchymal transition phenomenon.Methods： Immuohistochemistry was used to detect the expressions of Twist andHIF-1α in120cases of gastric carcinoma specimens and corresponding adjacentnormal tissue. Analysis the relationship between Twist, Hif-1α’s expression withclinical pathological parameters, postoperative survival time etc. and the relationshipwith the epithelial-mesenchymal transition phenomenon.Results： In gastric carcinoma HIF-1α, Twist, N-cad, E-cad positive rate was61.7%,59.1%,46.7%,37.5%, adjacent tissues, the positive rate was22.5%,18.3%,10.8%,91.7%. Tumor tissues and adjacent tissues there were significant differences (p <0.05).Patients with Twist positive expression showed higher incidence of lymph node metastasis (p<0.05) and distant metastasis (p<0.05) than those with Twist negativeexpression.Hif-1α expression was closely correlated with tumor histological type,depth of invasion, lymph node metastasis (p<0.05). Patients with high expression ofTwist and (or) Hif-1α had lower five-year survival rate than patients with negativeexpression. The expression of Twist and Hif-1α was significantly correlated in gastriccarcinoma accompanied by low expression of E-cad and abnormal high N-cadexpression (p <0.05).Conclusions: The expression of Hif-1α and Twist was closely related to the biologicalcharacteristics in gastric carcinoma; Hif-1α may promote epithelial mesenchymaltransition phenomenon, through up-regulation the expression of Twist, so that promoteinfiltration, metastasis of gastric adenocarcinoma. Objective: Observe the effect of inhibiting the expression of HIF-1α in gastric cancercell lines BGC-823through RNAi in epithelial to mesenchymal transition phenomenon.And investigate the role of HIF-1α in epithelial mesenchymal transition phenomenon,and its possible clinical application.Methods: Selection of human poorly differentiated gastric adenocarcinoma cell lineBCG-823cells for the study, using RNA interference, CoCl2induced hypoxia and othermethods to detect the expression of HIF-1α, TWIST protein and EMT related proteinE-cadherin, N-cadherin; Transwell chamber was used to detect cell’s abilities ofinvasion and metastasis.Result: After transient transfected BGC-823cells with psilencer3.0-HIF-1αrecombinant plasmids, the expression of HIF-1α in the average mRNA and proteinlevels was significantly inhibited; Twist, N-cad protein expression compared with CoCl2group was reduced and compared with control group in vitro the ability of invasion andmigration was significantly inhibited in RNAi group(p <0.05).Conclusions: HIF-1α siRNA expression vector can effectively inhibit the HIF-1α’sexpression in mRNA and protein levels; Induction of HIF-1α expression in hypoxiccondition was a key step in epithelial to mesenchymal transition in gastric cancer;HIF-1α could improve the efficacy of gastric cancer and can be used as a potentialtarget to extend their survival.