胃癌形成中细胞凋亡与Fas蛋白、P糖蛋白的表达及相关性研究

A Correlative Study on the Apoptosis and Expression of Fas Protein and P-glycoprotein in the Occurrence of Gastric Carcinoma

目的探讨癌前病变发展至胃癌过程中细胞凋亡、Fas蛋白、P糖蛋白 (P gp)表达的变化规律及相互关系。方法采用末端脱氧核苷酸转移酶 (TdT)介导的dUTP缺口原位末端标记法 (TUNEL)与免疫组织化学S P法 ,分别检测胃良恶性病变细胞凋亡指数 (AI)及Fas蛋白和P糖蛋白的表达。结果AI、Fas蛋白、P gp的表达在 30例慢性浅表性胃炎组、36例癌前病变组 (11例慢性萎缩性胃炎、12例重度肠上皮化生、13例中重度不典型增生 )中的比较差异无显著性 (P >0 .0 5 ) ;而在 36例癌前病变组与 32例胃癌组中的比较差异有显著性 (P <0 .0 5或P <0 .0 1) ,AI、Fas蛋白表达依次减少 ,P gp表达增加 ;AI与Fas表达呈正相关、与P gp呈负相关 (P <0 .0 1) ;Fas蛋白与P gp的表达呈负相关 (P <0 .0 1)。结论癌前病变转化成胃癌的过程与细胞凋亡和Fas蛋白、P gp的表达变化有关 ,Fas蛋白具有促凋亡作用 ,P gp具有抗凋亡、耐药的双重作用。

Objectives To explore the changing rule and inter relation in apoptosis and expression of Fas protein and P glycoprotein(P gp) during the developing course from precancerous lesions to gastric carcinoma. Methods Using terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) technique , the apoptotic indexes (AI) of gastric cells showing benign and malignant changes were detected ; while the expression of Fas protein and P gp was examined by immunohistochemical S P method. Results No statistical differences in AI and expression of Fas protein and P gp existed between group of chronic active superficial gastritis (30 cases) and group of precancerous lesions (36 cases 11 cases of chronic atrophic gastritis, 12 cases of severe intestinal metaplasia , and 13 cases of severe atypical hyperplasia )(P>0.05). However , statistical differences of AI , Fas protein and P pg expression were found between the group of precancerous lesions (36 cases)and group of gastric carcinoma(32 cases) (P<0.01 or P<0.05); AI and Fas protein expression decreased in order with an increase of P gp expression (P<0.01). AI showed a positive correlation with Fas protein expression and a negative correlation with P gp expression (P<0.01). There was a negative correlation between Fas protein and P gp expression (P<0.01). Conclusion The transformation from precancerous lesions to gastric carcinoma is related with cell apoptosis and changes in the expression of Fas protein and P gp. Fas protein can promote apoptosis, whereas P gp plays a dual role in anti apoptosis and drug tolerance.