选择性环氧合酶-2抑制剂Celebrex对胰腺癌血管内皮生长因子表达的影响

背景与目的:有研究证实,环氧合酶-2(cyclooxygenase-2,COX-2)与肿瘤,特别是与消化系统肿瘤形成的关系较为密切,而其抑制剂则具有抗肿瘤作用。本研究观察选择性COX-2抑制剂Celebrex对裸鼠胰腺癌PC-3细胞移植瘤血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)表达的影响。方法:观测Celebrex对裸鼠移植瘤生长的影响,并采用免疫组织化学、逆转录-聚合酶链反应(reversetranscriptionpolymerasechainreaction,RT-PCR)、蛋白免疫印迹(Westernblot)以及酶联免疫吸附测定(enzyme-linkedimmunosorbentassay,ELISA)检测裸鼠移植瘤组织中VEGF的表达。结果:给药组移植瘤生长曲线较对照组明显低平。对照组移植瘤体积为0.438cm3,给药组为0.212cm3(抑瘤率为51.6%,P<0.05)。给药组与对照组相比,VEGF表达明显减弱,ELISA显示,对照组VEGF表达量为(1.11±0.11)μg/g,给药组为(0.66±0.11)μg/g,VEGF抑制率为40.6%,两组间有显著性差异(P<0.05)。结论:COX-2可能参与了肿瘤新生血管的生成;选择性COX-2抑制剂Celebrex具有抑制肿瘤生长和对抗肿瘤新生血管生成的作用。

Effect of selective cyclooxygenase-2 inhibitor celebrex on expression of vascular endothelial growth factor (VEGF) in pancreatic carcinoma

BACKGROUND & OBJECTIVE: The previous study has identified that cyclooxygenase-2 (COX-2) may have a close relation with tumor genesis, particularly with digestive tract tumors, and its inhibitor can exert the chemoprevention role on carcinogenesis. This study was designed to investigate the effect of celebrex, a selective cyclooxygenase-2 inhibitor, on the expression of vascular endothelial growth factor (VEGF) in pancreatic carcinoma of xenografted nude mice induced by pancreatic carcinoma PC-3 cell lines. METHODS: The effect of celebrex on tumor growth was observed.The expression of VEGF in the tumors was determined by reverse transcription polymerase chain reaction (RT-PCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). RESULTS: Average tumor volume and tumor weight from control mice were 0.438+/-0.052 cm(3) and 0.552+/-0.064 g as compared with 0.215+/-0.038 cm(3) and 0.244+/-0.042 g from treated mice (inhibition rate:51.6%,P< 0.05). VEGF expression was significantly down-regulated in the celebrex-treated tumors. ELISA revealed that the expression levels of VEGF were 1.11+/-0.11(microg/g) in control mice and the 0.66+/-0.11(microg/g) in the treated mice. The inhibition rate of VEGF was 40.6% (P< 0.05). CONCLUSION: COX-2 may play an important role in the angiogenesis of pancreatic carcinoma. The selective COX-2 inhibitor, celebrex, can result in the inhibition of angiogenesis and tumor growth.