环氧合酶-2与P-糖蛋白在人肝癌细胞中的表达及其意义

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

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RT—PCR、免疫组织化学方法分别检测COX-2mRNA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1mRNA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爿。检验、用精确概率法分析组间差异，样本间均数的比较用f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％，X^2=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％，x^2=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％，X^2=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％，X^2=64．42，P〈0．01）。RT—PCR检测结果显示COX-2mRNA在正常肝组织中无表达，而多药耐药基因1mRNA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。

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 fi＇om 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 = 7.5 l, 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 Cox- 2 gene might involved in the multidrug resistance of the hepatocellular carcinoma mediated by P-gp.