环氧合酶2抑制剂的抗胰腺癌作用及相关机制

Anti-tumor effect and mechanism of cyclooxygenase 2 inhibitor in pancreatic cancer

目的探讨环氧合酶2(COX-2)抑制剂对胰腺癌细胞增殖、侵袭、迁移能力和对COX-2、基质金属蛋白酶(MMP)-14蛋白表达的影响以及可能的抗胰腺癌机制。方法不同浓度的COX-2抑制剂塞来昔布(20、60、100μmol/L)处理胰腺癌细胞后,用MTT比色法检测细胞的增殖能力;用Transwell侵袭实验和划痕实验检测细胞的侵袭能力和迁移能力;ELISA检测MMP-14和COX-2的蛋白表达情况。结果 MTT增殖实验、Transwell侵袭实验、划痕实验分别提示,COX-2抑制剂作用后胰腺癌细胞的增殖、侵袭、迁移能力均以浓度梯度形式下降(P<0.05);ELISA结果显示,胰腺癌细胞中COX-2和MMP-14的蛋白表达水平相应降低(P<0.05),两者表达具有显著正相关性(r=0.873,P<0.05)。结论 COX-2抑制剂可能通过抑制COX-2表达下调MMP-14表达,进而以浓度梯度形式减弱胰腺癌细胞的增殖、侵袭、迁移能力,起到抗胰腺癌作用。

Objective To investigate the effect of COX-2 inhibitor on proliferation, migration, invasion and the expression of COX-2, matrix metalloproteinase （MMP） -14 in pancreatic cancer cell and its possible anti-tumor mechanism. Methods Human pancreatic cancer cell line PANC-1 was treated with diverse concentrations of COX-2 inhibitor celebrex （20, 60, 100μmol/L）. Cell proliferation, invasion and migration capabilities were measured by MTT colorimetry, Transwell invasion assay, and scratch assay. The protein expression of COX-2 and MMP-14 was assessed by ELISA. Results The proliferation, invasion and migration capabilities were decreased in a concentration-dependent manner by COX-2 inhibitor （P 〈 0.05 ）. The protein expression of COX-2 and MMP-14 was correspondingly reduced （ P 〈 0. 05 ）. MMP-14 expression was positively correlated with COX-2 expression （ r =0. 873 ,P 〈 0. 01 ）. Conclusion COX-2 inhibitor may down-regulate MMP-14 expression via inhibiting COX-2 expression, then attenuating the proliferation, invasion and migration of human pancreatic cancer cell in a concentration-dependent manner, contributing to its anti-tumor effect in pancreatic cancer.