环氧合酶-2与P-糖蛋白在人肝癌细胞中的表达及其意义

目的 探讨环氧合酶(COX)-2在肝细胞癌发生、发展中的作用及其对P-糖蛋白(P-gp)表达的影响. 方法 收集2003年10月-2005年6月因肝癌切除术切取的肝癌组织标本,用RTPCR、免疫组织化学方法分别检测COX-2 mRNA和COX-2蛋白在肝癌组织和腹部手术取得的正常肝组织中的表达.同时检测多药耐药基因1 mRNA和P-gp在肝癌组织中的表达情况,并分析COX-2与P-gp在肝癌组织中表达的相关性.各样本率间比较采用x2检验、用精确概率法分析组间差异,样本间均数的比较用t检验,用Spearman' s等级相关公式分析COX-2和P-gp的相关性.结果 共收集肝癌组织52例,正常肝组织20例.正常肝组织中未见COX-2表达,COX-2表达在中、低分化肝癌组织的阳性率(94.1％)高于高分化肝癌组织(38.9％,x2= 6.80,P＜0.01);在HBsAg阳性的肝癌组织中的表达(91.7％)高于HBsAg阴性的肝癌组织(62.5％,x2= 4.70,P＜0.05);在合并肝硬化的肝癌组织中的表达(96.7％)高于无肝硬化的肝癌组织(63.6％,x2= 7.51,P＜0.01);P-gp在癌组织中的表达(86.6％)高于相应的癌旁组织(30.7％,x2= 64.42,P＜0.01).RT-PCR检测结果显示COX-2 mRNA在正常肝组织中无表达,而多药耐药基因l mRNA在肝癌组织和正常肝组织中均有表达.同时表达COX-2和多药耐药基因1为42例,两者呈正相关(r=0.563,P＜0.01).结论 本研究结果提示COX-2参与了以P-gp介导的肝癌的多药耐药机制.

Expressions and significance of COX-2 and P-gp in human hepatocellular cacinoma tissues

Objective To investigate the effect of the COX-2 gene on the oncogenesis and development of the hepatocellular cacinoma and the influence of COX-2 gene on the expression of P-gp protein.Method Fifty-two pieces of the hepatocellular cacinoma samples and 20 cases of normal liver samples were collected from the patients operated from October 2003 to June 2005.RT-PCR and immunohistochemistry staining were employed to detect the COX-2 mRNA as well as P-gp protein in the normal liver tissues and the carcinoma tissues.Meanwhile,the expression of the mdr 1 mRNA in the carcinoma tissues was also determined and the correlation between the expressions of the COX-2 and P-gp was investigated.Results No expression of the COX-2 in the normal liver tissue was detected.The positive expression of COX-2 in the low and middle differentiated carcinoma was elevated significantly as compared with that in the high differentiated carcinoma tissue (x2 = 6.80,P ＜ 0.01).The positive expression of the COX-2 in the HBSAg (+) carcinoma tissue was significantly higher as compared with that in the HBSAg (-) carcinoma ( x2= 4.70,P ＜ 0.05),and the carcinoma in combination with cirrhosis also showed significantly higher in expression of COX-2 than the carcinoma without cirrhosis (x2 = 7.51,P ＜ 0.01).The mdrl mRNA was found both expressed in the normal and carcinoma tissues.The expression of COX-2 mRNA was found in the carcinoma,but not found in the normal tissues.The COX-2 mRNA and mdrl mRNA was found both expressed in the normal and carcinoma tissues.The correlation coefficient between COX-2 and mdrl mRNA was 0.563 (P ＜ 0.01).Conclusion The results indicated that Cox2 gene might involved in the multidrug resistance of the hepatocellular carcinoma mediated by P-gp.