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

Expressions of COX-2,VEGF,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

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<0.05)。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-9proteins 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-3 were 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.