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

点击翻译按钮获取中文摘要

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.