胃癌组织中Sonic Hedgehog表达及其与NF-kappaB的关系研究

The Expression of Hedgehog and its Correlation with the Expression of NF-kappaB in the Tissues from Gastric Carcinoma

目的探讨Hedgehog在胃癌及其癌前病变中的表达及与NF-kappaB的关系。方法选择50例萎缩性胃炎、46例肠化生和57例胃癌患者的胃黏膜内镜活检样本,同时选择30例正常人作为对照;分为萎缩性胃炎组、肠化生组、胃癌组和正常黏膜组。通过病理学检测患者Hpylori感染状况。免疫组化法检测Hedgehog和NF-kappaB在不同阶段胃癌组织中的表达差异。流式细胞仪分析各组胃黏膜细胞的周期分布和凋亡率。Western blot检测Hedgehog表达。结果在胃癌的发展过程中,胃黏膜组织中Hedgehog表达水平先降低后升高。NF-kappaB表达水平在正常胃组织、萎缩性胃炎和肠化生组织中无明显变化,但在胃癌组织中表达显著增强。与正常胃黏膜组织比较,萎缩性胃炎、肠化生和胃癌组织中的S期细胞比例更高。细胞凋亡率萎缩性胃炎组和肠化生组较高,而胃癌组较低。抑制NF-kappaB后,Hedgehog蛋白在胃癌组织中的表达降低。结论在胃癌的发展过程中,Hedgehog蛋白表达水平先降低后升高。H pylori感染可能通过激活NF-kappaB,继而增强Hedgehog表达,同时赋予胃癌细胞凋亡抵抗。

Objective To explore the expression of Hedgehog in gastric carcinoma and precancerous lesions and the relationship between Hedgehog and NF-kappaB.Methods Gastric endoscopic biopsy samples of 50 cases of atrophic gastritis,46 cases of intestinal metaplasia and 57 cases of gastric cancer were selected for study.30 cases of healthy persons were selected as control.All samples were divided into atrophic gastritis,intestinal metaplasia,gastric cancer and normal control groups.H pylori infection status of patients was analyzed by histopathology method..Immunohistochemistry was used to detect Hedgehog and NF-kappaB expression at different stages of gastric cancer progression.Flow cytometry was used to analyze cell cycle phase and apoptosis of gastric mucosal cells of all groups.The expression difference of Hedgehog was detected by western blot after treatment of NF-kappaB inhibitor.Results In the course of development of gastric cancer,Hedgehog expression in the gastric mucosa increased after the reduction firstly.There were no significant change of NF-kappaB expression between atrophic gastritis or intestinal metaplasia and normal control.However,NF-kappaB expression was markedly increased in gastric cancer.The percentage of S phase of the cell cycle was significantly higher in atrophic gastritis,intestinal metaplasia,and gastric cancer,compared to normal mucosa cells.Apoptosis rate was significantly higher in atrophic gastritis and intestinal metaplasia,but was lower in gastric cancer group.Conclusion In the process of development of gastric cancer,Hedgehog protein expression shows increased after a first reduction process.The mechanism may lie in the activation of NF-kappaB due to H.pylori infection,which further enhances Hedgehog expression apoptosis resistance of gastric cancer cells.