2002 Fiscal Year Final Research Report Summary
Study on growth suppression of lung cancer by inhibitors of arachidonic acid metabolism
Project/Area Number |
13670625
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Aichi Cancer Center Research Institute |
Principal Investigator |
HIDA Toyoaki Research Institute, Researcher, 研究所, 研究員 (80250249)
|
Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Takashi Molecular Oncology, Chief, 分子腫瘍学部, 部長 (50231395)
|
Project Period (FY) |
2001 – 2002
|
Keywords | Arachidonic acid / Cyclooxygenase 2 / Lung cancer / Chemotherapy / Growth suppression / COX-2 inhibitor / Combination / Clinical application |
Research Abstract |
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.
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Research Products
(12 results)