胰腺癌组织 COX-2、VEGF、MMP-9的表达及塞来布昔对人胰腺癌 BXPC-3细胞 VEGF、MMP-9表达的影响

摘要

目的：观察胰腺癌组织环氧合酶-2（COX-2）、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）的表达及塞来布昔对人胰腺癌BXPC-3细胞VEGF、MMP-9表达的影响。方法采用免疫组织化学SP法检测COX-2、VEGF、MMP-9在50例原发性胰腺癌及癌旁正常组织的表达，分析其与胰腺癌临床病理特征的关系。实时荧光定量PCR法（ RT-QPCR）和Western blot检测塞来布昔对BXPC-3细胞VEGF、MMP-9 mRNA和蛋白表达的影响。结果COX-2、VEGF、MMP-9在胰腺癌组织的阳性表达率显著高于癌旁组织，差异有统计学意义（ P ＜0 V．05）。 COX-2、VEGF、 MMP-9高表达与胰腺癌增殖活性、TNM临床分期及肿瘤浸润转移等临床病理特征相关（ P ＜0．05），而与年龄、性别、发病部位、病理组织分级无关（ P ＞0．05）；且COX-1与VEGF、MMP-9表达呈正相关性（ P ＜0．05）。随着塞来布昔剂量的增高，BXPC-3细胞VEGF、MMP-9 mRNA和蛋白表达均降低，与对照组比较差异有统计学意义（ P ＜0．05）。结论 COX-2、VEGF、MMP-9胰腺癌组织表达增高，可能在肿瘤发生发展中发挥重要作用；COX-2特异性抑制剂塞来布昔可能通过下调VEGF、MMP-9的表达发挥抗肿瘤作用。%Objective To investigate the expressions of cyclooxygenase-2 ( COX-2 ) , vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) in pancreatic cancer tissue and the effects of celecoxib on expression of VEGF and MMP-9 in human pancreatic cancer cell line BXPC-3.Methods The expression levels of COX-2, VEGF, MMP-9 proteins were detected by immunohistochemistry ( SP) in 50 cases of primary pancreatic cancer tissue and adjacent normal tissues,moreover, the correlation between the expressions of COX-2, VEGF, MMP-9 and clinicopathological characteristics of pancreatic cancer was analyzed.The effects of celecoxib on expressions of VEGF and MMP-9 mRNA and proteins in human pancreatic cancer cell line BXPC-3 were detected by RT-QPCR and Western Blot.Results The expression levels of COX-2, VEGF, MMP-9 in pancreatic cancer tissue were significantly higher than those in adjacent normal tissue ( P <0.05 ) .The expressions of COX-2, VEGF, MMP-9 were closely correlated to proliferative activity, tumor metastasis and clinical stage of pancreatic carcinoma ( P <0.05), however,which were not related with patient’ s age and gender, anatomical site and histological grade of pancreatic carcinoma,furthermore, the expression of COX-2 was positively correlated to that of VEGF or MMP-9 ( P <0.05).With the increase of celecoxib dosage ,the expression levels of VEGF, MMP-9 mRNA and protein in pancreatic cancer cell line BXPC-3were significantly decreased , as compared with those in control group ( P <0.05 ) . Conclusion The high expression of COX-2, VEGF, MMP-9 in pancreatic carcinoma may play an important role in pathogenesis and progression of pancreatic carcinoma.Celecoxib may develop antitumor effects through down-regulating the expressions of COX-2, MMP-9 and VEGF.