Basic study on anti-tumor activity of non-vitamin K dependent oral anticoagulants (NOACs)

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08633
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: SUZUKI Koji 鈴鹿医療科学大学, 薬学部, 教授 (70077808)
• Research Collaborator: HIRAMOTO Keiichi ; HAYASHI Tatsuya ; OKAMOTO Takayuki ; NISHIOKA Junji ; AKITA Nobuyuki ; TERASAWA Masahiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗凝固薬 / NOACs / Xa因子阻害薬 / Xa因子受容体 / 抗腫瘍作用 / 抗転移作用 / 大腸癌細胞 / メラノーマ細胞

Outline of Final Research Achievements

Non-vitamin K-dependent oral anticoagulants (NOACs) are used as preventives for cerebral thromboembolism and deep vein thrombosis in the lower limbs. In this study, we analyzed the antitumor effects of NOACs. Anti-thrombin drug (dabigatran etexilate) and anti-Xa drug (edoxaban, rivaroxaban) are orally administered daily to tumor-bearing mice to which colon cancer cells Colon-26 cells have been transplanted, and blood and tumor tissue obtained from mice on day 21 were collected and analyzed. As a result, edoxaban dose-dependently suppressed the growth of tumor cells, the expression of IL-6 and MMP-2 in blood, the expression of cell membrane factor Xa receptor (PAR2) of tumor tissue, and the expression of cell division-related factors. Edoxaban also promoted apoptosis of cells of the tumor tissue.

Free Research Field

血栓止血学

Academic Significance and Societal Importance of the Research Achievements

現在、癌患者数は増加の一途にあり、これまでにない新しい視点からの癌の発生や増殖・転移阻止の方策の確立が求められている。私はこれまでの血栓止血学研究の経験から、血液の流動性維持に重要な凝固制御系因子が癌細胞の増殖や転移を抑制する可能性を示してきた。そこで本研究では、癌細胞の増殖と転移に及ぼす経口抗凝固薬NOACsの影響とその作用機序を解析し、NOACsが癌細胞の増殖と転移を抑制することを示し、その作用機序の一端を明らかにすることができた。本研究で得られた成果は学術的にも重要であり、癌制御に向けた社会的意義は非常に大きいと考えられる。