Department of Gastroenterology, Affiliated Hospital of Nantong University, Nangtong, Jiangsu 226001, China.
Biomed Pharmacother. 2011 Oct;65(7):486-90. doi: 10.1016/j.biopha.2011.06.009. Epub 2011 Aug 27.
Cyclooxygenase (COX)-2 and lipoxygenase (LOX)-5 are involved in carcinogenesis of pancreatic cancer. COX-2 inhibitor celecoxib displays inhibitory effects in pancreatic cancer cell growth. Recently, it has been reported that COX-2 inhibitor may not be able to suppress pancreatic tumor growth in vivo and its application is further limited by untoward side effects. The present study provides evidence that combined use of celecoxib and 5-LOX inhibitor MK886 markedly suppresses pancreatic tumor cell growth in vitro. Compared to the single inhibitor treatment, dual treatment with celecoxib and MK886 exerted additive antitumor effects in pancreatic tumor cells. We found that MK886 reversed celecoxib-induced increases in 5-LOX gene expression and Erk1/2 activation in pancreatic tumor cells. Moreover, Dual treatment of pancreatic tumor cells with celecoxib and MK886 inhibited the levels of LBT4 receptor BLT1 and vascular endothelial growth factor. Our results imply that combined use of celecoxib and MK886 might be an effective way to treat clinical patients with pancreatic cancer.
环氧化酶（COX）-2 和脂氧合酶（LOX）-5 参与胰腺癌的发生。COX-2 抑制剂塞来昔布在胰腺癌细胞生长中显示出抑制作用。最近，有报道称 COX-2 抑制剂在体内可能无法抑制胰腺肿瘤的生长，其应用进一步受到不良反应的限制。本研究提供的证据表明，塞来昔布和 5-LOX 抑制剂 MK886 的联合使用可显著抑制体外胰腺肿瘤细胞的生长。与单一抑制剂治疗相比，塞来昔布和 MK886 的双重治疗在胰腺肿瘤细胞中发挥了相加的抗肿瘤作用。我们发现 MK886 逆转了塞来昔布诱导的胰腺肿瘤细胞中 5-LOX 基因表达和 Erk1/2 激活的增加。此外，塞来昔布和 MK886 双重处理胰腺肿瘤细胞可抑制 LBT4 受体 BLT1 和血管内皮生长因子的水平。我们的研究结果表明，塞来昔布和 MK886 的联合使用可能是治疗临床胰腺癌患者的有效方法。
