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

Effect of Selective Cyclooxygenase-2 Inhibitor Celebrex on Expression of Vascular Endothelial Growth Factor (VEGF) in Pancreatic Carcinoma

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。

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 cm3 and 0.552±0.064 g as compared with 0.215±0.038 cm3 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(μg/g) in control mice and the 0.66±0.11(μg/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.