| Project/Area Number |
18K07001
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 胆道癌 / アミノ酸トランスポーター / 抗がん剤 / LAT1 |
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| Outline of Final Research Achievements |
The expression of LAT1 and LAT2 was confirmed for human biliary tract cancer cell lines by cell block immunostaining, Real time RT-PCR and western blotting. Of these, TFK1 showed high LAT1 expression and appropriate cell proliferation, therefore we investigated the cell proliferation inhibitory effects of LAT1 novel inhibitor JPH203, Gemcitabine and mTOR molecular therapeutic agent Everolimus. The cell growth inhibitory effect was stronger in the order of Gemcitabine> JPH203 / Everolims, and the effect was enhanced by co-administration. Multiple LAT1 knockdown cell lines were prepared by both siRNA and shRNA using lentivirus vector, and the decrease in LAT1 expression was confirmed. Further experiments are currently underway.
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| Academic Significance and Societal Importance of the Research Achievements |
以前我々は胆道癌において正常上皮よりもLAT1が発現亢進し、その高発現は独立した有意な予後不良因子であることを報告した（Cancer Med., 2014）。今回我々はLAT1高発現で新規阻害薬JPH203での効果が期待され、かつ悪性度の高い胆道癌細胞株について、新規LAT1選択的阻害薬JPH203による腫瘍抑制効果を確認した。また現在胆道癌の標準的治療薬のひとつであるゲムシタビン、あるいはLAT1下流経路であるmTORの分子標的阻害薬エベロリムスの共投与によって追加の抗腫瘍効果を認めた。LAT1を新たな標的としたがん治療の臨床応用のための基礎的データが得られた。
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