硫氧还原蛋白与氧化应激在胃癌中表达水平和意义

Role of oxidative stress and thioredoxin in gastric cancer

目的探讨氧化应激和抗氧化蛋白-硫氧还原蛋白(Trx)在胃癌发生发展中的作用。方法采用紫外分光光度法测定胃癌患者(n=48)和健康自愿者(n=30)血浆中腺苷脱氨酶(ADA)、谷胱苷肽过氧化物酶(GPX)、超氧化物歧化酶(SOD)、晚期蛋白氧化产物(AOPP)的表达水平,采用酶联免疫吸附法(ELISA)测定硫氧还原蛋白的表达水平;采用荧光定量RT-PCR法测定胃癌组织(n=68)和其癌周正常组织中Trx mRNA的表达水平。结果胃癌组血浆ADA、AOPP的表达水平高于对照组(P<0.05),GPX表达明显低于对照组(P<0.05),SOD在两组间未见明显差异。胃癌组血浆Trx表达水平明显高于健康对照组(P<0.05),Trx表达水平与远处转移有关(P<0.05)。胃癌与正常胃组织Trx mRNA水平比较差异具有统计学意义(P<0.05)。结论胃癌患者存在过高的氧化应激水平,胃癌组织Trx mRNA相对表达值高,血浆硫氧还原蛋白高表达且与肿瘤远处转移有关。

Objective To explore the role of oxidative stress and the antioxidant protein thioredoxin in the tumorigenesis and progression of gastric cancer.Methods The plasma levels of adenosine deaminase（ADA）,glutathione peroxidase（GPX）,superoxide dismutase（SOD）,and advanced oxidation protein products（AOPP） were determined by colorimetry,and the plasma levels of thioredoxin were determined by enzyme-linked immunosorbent assay（ELISA） in 48 gastric cancer patients and 30 healthy subjects.RT-PCR assay was employed to examine the expression levels of thioredoxin mRNA in the tissue samples of the patients.Results Compared with the healthy controls,patients with gastric cancer had significantly increased plasma levels of ADA and AOPP（P〈0.05）,decreased plasma GPX level（P〈0.05）,and similar plasma SOD levels.The plasma levels of thioredoxin were significantly higher in patients with gastric cancer than in the healthy controls（P〈0.05）.Thioredoxin levels was not associated with gender,age,degree of tumor cell differentiation,invasion depth,or lymph node metastasis（P〉0.05）,but was correlated to distant tumor metastasis（P〈0.05）.The expression of Trx mRNA was significantly higher in gastric carcinoma than in normal gastric tissue（P〈0.05）.Conclusion Gastric cancer patients have high levels of oxidative stress and thioredoxin expression,and the latter is related to distant metastasis of the tumor.