Study on growth suppression of lung cancer by inhibitors of arachidonic acid metabolism

由花生四烯酸合成洋地黄素的限速酶是环氧合酶（考克斯）。最近的研究表明考克斯-2在肺癌中表达上调。考克斯-2在肿瘤组织中的优先表达表明，这种酶可能为癌症治疗提供一个潜在的靶点。本研究旨在探讨考克斯-2抑制剂在肺癌中的作用。选择性考克斯-2抑制剂JTE-522单药在体外和体内均能抑制人肺癌细胞的生长。此外，辅助使用考克斯-2抑制剂显示出不仅在体外而且在体内显著增强常规抗癌药物的治疗功效，而不引起任何明显的副作用。实际上，<50>各种抗癌剂的体外IC_值降低高达70%，而考克斯-2抑制剂与多西他赛和长春瑞滨的联合治疗在体内分别抑制肿瘤生长65%和55%。另外，考克斯-2抑制剂在体内部分通过抑制肿瘤血管生成而影响肿瘤生长。这些发现表明，使用选择性考克斯-2抑制剂治疗肺癌可能是有希望的，特别是因为它增强了传统抗癌药物的治疗效果，而不影响生活质量。

The rate-limiting enzyme in the synthesis of prostaglandins from arachidonic acid is cyclooxygenase (COX). Recent studies have shown COX-2 expression to be up-regulated in lung cancer. The preferential expression of COX-2 in tumors versus normal tissues suggests that this enzyme may provide a potential target for cancer therapy. In this study, we examined the effects of COX-2 inhibitor in lung cancer. A selective COX-2 inhibitor, JTE-522, inhibited both in vitro and in vivo growth of human lung cancer cells as a single agent. Furthermore, the adjunct use of COX-2 inhibitor were shown to significantly enhance treatment efficacy of conventional anticancer drugs not only in vitro but also in vivo without causing any noticeable side-effects. Indeed, IC_<50> values of various anticancer agents in vitro were reduced by up to 70%, while the combination therapy of COX-2 inhibitor with docetaxel and vinorelbine inhibited tumor growth in vivo by 65% and 55%, respectively. In addition, COX-2 inhibitor affected tumor growth in vivo in part by inhibiting tumor angiogenesis. These findings suggest that the use of a selective COX-2 inhibitor in the treatment of lung cancer may be promising, especially because of its enhancement of the treatment efficacy of conventional anticancer agents without compromising quality of life.