Enhancing antitumor effects in pancreatic cancer cells by combined use of COX-2 and 5-LOX inhibitors
Enhancing antitumor effects in pancreatic cancer cells by combined use of COX-2 and 5-LOX inhibitors
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DOI：
10.1016/j.biopha.2011.06.009
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发表时间：
2011-10-01
影响因子：
7.5
通讯作者：
Zhou, Guoxiong
中科院分区：
文献类型：
--
作者：
Ding, Xiaoling;Zhu, Chen;Zhou, Guoxiong
环氧合酶（考克斯）-2和脂氧合酶（LOX）-5参与胰腺癌的发生。考克斯-2抑制剂塞来昔布对胰腺癌细胞生长有抑制作用。近年来，有报道称，考克斯-2抑制剂在体内可能不能抑制胰腺肿瘤的生长，并且其应用受到不良副作用的进一步限制。本研究提供的证据表明，塞来昔布和5-LOX抑制剂MK 886联合使用显着抑制胰腺癌细胞的生长在体外。与单一抑制剂治疗相比，塞来昔布和MK 886的双重治疗在胰腺肿瘤细胞中产生了相加的抗肿瘤作用。我们发现MK 886逆转了塞来昔布诱导的胰腺肿瘤细胞中5-LOX基因表达和Erk 1/2激活的增加。此外，用塞来昔布和MK 886双重处理胰腺肿瘤细胞抑制LBT 4受体BLT 1和血管内皮生长因子的水平。提示塞来昔布联合MK 886治疗胰腺癌可能是一种有效的治疗方法。(C)2011年Elsevier Masson SAS。All rights reserved.
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. (C) 2011 Elsevier Masson SAS. All rights reserved.