COX-2调节HIF-1α和VEGF在人胰腺癌中的表达

Regulation of HIF-1α and VEGF in human pancreatic carcinoma by COX-2

目的检测环氧合酶-2、低氧诱导因子-1α和血管内皮生长因子在胰腺癌组织中的表达情况，并进一步研究选择性环氧合酶-2抑制剂尼美舒利对胰腺癌BxPC-3细胞株中这3种蛋白表达的影响，探讨环氧合酶-2在胰腺恶性肿瘤血管生成过程中的作用及意义。方法应用Western blotting检测12例胰腺癌及相应癌旁组织中环氧合酶-2、低氧诱导因子-1α和血管内皮生长因子蛋白的表达情况，应用不同浓度（分别为DMSO组，50／μmol／L，100μmol／L组和200μmol／L组）尼美舒利作用于BxPC-3细胞24h后，提取细胞蛋白行Western blotting，观察3种蛋白表达水平的变化。结果12例胰腺癌组织标本中均检测到有环氧合酶-2蛋白的高表达，相比之下，癌旁组织中则相对低表达甚至未表达，低氧诱导因子-1a和血管内皮生长因子蛋白也存在相同情况，即在癌组织中的表达要明显高于癌旁组织。而在尼美舒利不同浓度作用于胰腺癌BxPC-3细胞后，可明显抑制3种蛋白的表达水平（P〈0．01），并呈剂量依赖性。结论胰腺癌组织中环氧合酶-2、低氧诱导因子-1a和血管内皮生长因子呈过量表达，提示环氧合酶-2可能与胰腺肿瘤血管生成有关，而选择性环氧合酶-2抑制剂尼美舒利可抑制这3种蛋白的表达水平，这可能为其抗肿瘤新生血管形成的机制之一。

Objective To detect the expression of cyclooxygenase-2 （COX-2）, hypoxia inducible factor -1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF） in pancreatic carcinoma, investigate effect of nimesulide, a COX-2-selected inhibitor, of various concentrations on the expression of the 3 proteins and explore the relation of COX 2 expression to angiogenesis. Methods The expression of COX-2, HIF-la and VEGF in 12 cases of pancreatic carcinoma and corresponding paracarcinoma tissues were detected by western blotting. The effect of nimesulide of different concentrations on expression of the 3 proteins was also determined by Western blotting. Results The expression level of the 3 proteins was significantly higher in the pancreatic carcinoma than in paracarcinoma tissues. Meanwhile, nimesulide of various concentrations significantly reduced the expression level of the 3 proteins. Conclusion Over-expression of COX-2 might be responsible for increase of HIF-1α and VEGF production in pancreatic carcinoma, which suggests that COX-2 may be related to tumor anglogenesis. Furthermore, COX-2-selected inhibitor nimesulide can inhibit expression of HIF-1α and VEGF in pancreatic carcinoma.