| Project/Area Number |
17H01602
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Chiba University |
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Principal Investigator |
Tanzawa Hideki 千葉大学, 大学院医学研究院, 教授 (50236775)
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| Co-Investigator(Kenkyū-buntansha) |
坂本 洋右 千葉大学, 医学部附属病院, 講師 (50451745)
皆川 康之 千葉大学, 大学院医学研究院, 特任助教 (30639787)
小河原 克訓 千葉大学, 大学院医学研究院, 特任研究員 (20372360)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥42,900,000 (Direct Cost: ¥33,000,000、Indirect Cost: ¥9,900,000)
Fiscal Year 2019: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2018: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2017: ¥21,060,000 (Direct Cost: ¥16,200,000、Indirect Cost: ¥4,860,000)
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| Keywords | 口腔扁平上皮癌 / ALY / GAD1 / HTR2C / KLK13 / βcatenin / Wnt / Cadherin / カテニン / Wnt経路 / カドヘリン複合体 / カドヘリン / catenin / Lin7C |
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| Outline of Final Research Achievements |
We previously identified the cell adhesion-related genes (ALY, GAD1, KLK13, and HTR2C) and their specific inhibitors (mirtazapine, mercaptopropionic acid, ruboxistaurin, and chlorogenic acid) as candidate drugs for anti-metastasis. In this study, we investigated the tumor metastasis activities in vitro and in vivo using the knockdown of adhesion-related genes and the specific inhibitors. In addition to the data of transfectants, invasion and migration activities were significantly reduced after treatment of cancer cell lines with the inhibitors. Furthermore, lower metastatic capacity to other organs was observed in the cancer-transplanted mice after peritoneal injection with the inhibitors. Therefore, our results suggested that the specific inhibitors of cell adhesion-related genes would be novel therapeutic agents for clinical cancer research field.
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| Academic Significance and Societal Importance of the Research Achievements |
癌転移の抑制が実現すれば飛躍的な癌治療成績の向上が期待できるが、この現在の最重要課題に関し、有効な薬剤は未だ開発されていない。本研究では,口腔扁平上皮癌、腺癌、悪性黒色腫に対して転移抑制候補薬剤（クロロゲン酸、ルボキシスタウリン、3MPA、ミルタザピン）を同定しin vivoの転移抑制実験まで行った。クロロゲン酸、ルボキシスタウリン、3MPA、ミルタザピンに関して、組織への転移に関して有意な差を認めた。これらの薬剤は実際の臨床で癌以外の疾患で用いられている薬剤であるため、人体に対する安全性が高く、臨床応用の可能性が高いものと考えられる。
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