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

花生四烯酸合成前列腺素的限速酶是环氧合酶(COX)。最近的研究表明，COX-2在肺癌中的表达上调。与正常组织相比，COX-2在肿瘤组织中优先表达，提示该酶可能为肿瘤治疗提供一个潜在的靶点。在这项研究中，我们研究了COX-2抑制剂在肺癌中的作用。选择性COX-2抑制剂JTE-522可作为单一药物抑制人肺癌细胞的体外和体内生长。此外，COX-2抑制剂的辅助使用不仅在体外，而且在体内都能显著提高传统抗癌药物的治疗效果，而不会引起任何明显的副作用。事实上，各种抗癌药物在体外的IC50和GT；值都降低了70%，而COX-2抑制剂与多西紫杉醇和长春瑞滨联合治疗后，体内肿瘤生长分别抑制了65%和55%。此外，COX-2抑制剂在体内影响肿瘤生长的部分原因是通过抑制肿瘤血管生成。这些发现表明，选择性COX-2抑制剂在肺癌治疗中可能是有前景的，特别是因为它在不影响生活质量的情况下增强了传统抗癌药物的治疗效果。

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.