2022 Fiscal Year Final Research Report
Synergistic Effects of LAT1 and Glut1 Inhibitors against Anaplastic Thyroid Cancer in Vitro
| Project/Area Number |
20K08939
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大谷 真喜子 和歌山県立医科大学, 医学部, 講師 (00795594)
玉川 俊次 和歌山県立医科大学, 医学部, 講師 (40543781)
熊代 奈央子 和歌山県立医科大学, 医学部, 助教 (50746435)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Glut1 / LAT1 |
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| Outline of Final Research Achievements |
Using anaplastic thyroid carcinoma and cell lines, we explored the relationship between molecular target therapy by the interaction of various glucose transporter inhibitors and LAT1 administration and HIF2a, an upstream counter.
In a cell proliferation test, combination of LAT1 inhibition and Glut1 inhibition suppressed strong tumor growth. Decreased expression of MIB1 was observed. Western blot showed that Glut1 inhibition resulted in LAT1 expression, and conversely, LAT1 inhibition resulted in Glut1 expression, which differed depending on the cell line. Knockdown of HIF2a with miRNA reduced LAT1 expression and decreased tumor growth.
We demonstrated that dual inhibition of LAT1 and Glut1 could lead to cancer regulation. It was suggested that it may be mediated by HIF2a mechanism.
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| Free Research Field |
癌
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| Academic Significance and Societal Importance of the Research Achievements |
甲状腺未分化癌は、１年生存率が30%以下の極めて予後不良な高悪性度癌の一つである。治療法は外科的治療に加え、近年開発がすすむ分子標的治療が行われる。分子標的治療は単剤使用で、耐性を生じる為、数年は病状を安定させるもその後は増悪が予想される。本研究を通じ、甲状腺未分化癌の二重阻害による新しい治療方法を模索する事が出来た。
今までに無いメカニズムからの癌細胞制御の結果から、新しい治療を求めている甲状腺未分化癌患者にとって非常に有意義である。一連の研究から得られた知見で、今後の橋渡し研究を経て臨床薬剤の開発、治験へと結び付く可能性があると考えられる。
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