2023 Fiscal Year Final Research Report

Development of a new treatment for lymphatic malformations with COX-2 inhibitors

Research Project

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Project/Area Number	21K07851
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 52050:Embryonic medicine and pediatrics-related
Research Institution	Kagoshima University
Principal Investigator	Okamoto Yasuhiro 鹿児島大学, 医歯学域医学系, 教授 (30398002)
Co-Investigator(Kenkyū-buntansha)	児玉祐一鹿児島大学, 医歯学域鹿児島大学病院, 講師 (20535695) 中川俊輔鹿児島大学, 医歯学総合研究科, 特任助教 (60789973) 西川拓朗鹿児島大学, 医歯学域鹿児島大学病院, 講師 (90535725)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	リンパ管奇形 / COX-2阻害薬
Outline of Final Research Achievements	After experiencing patients where a COX-2 inhibitor was effective as a treatment for lymphatic malformation (LM), this study aimed to confirm that COX-2 promotes lymphatic endothelial cell proliferation in vitro and determine whether COX-2 inhibitors inhibit it. We then sought to elucidate the molecular biological mechanisms by which COX-2 inhibitors suppress LM. We found that COX-2 promotes cell proliferation and tube formation via VEGF in primary cultured lymphatic endothelial cells and a newly generated LM cell line; the effects of COX-2 inhibitors are rescued by downstream PGE2 and VEGF120, and COX-2 inhibitors inhibit PGE2 and VEGF120-mediated suppression of tube formation.
Free Research Field	小児血液、小児がん
Academic Significance and Societal Importance of the Research Achievements	本研究においてCOX-2がリンパ管奇形の増殖の中心的な役割を果たしていること、COX-2阻害薬がリンパ管奇形の増殖を抑制する分子機序を明らかにしたことは本研究の学術的意義である。本研究を元に、COX-2阻害薬を実臨床へ応用する薬剤の開発が進めば社会的意義は大きい。