| Project/Area Number |
18K15627
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52040:Radiological sciences-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 細胞老化 / 放射線療法 / 食道癌 / メトホルミン / 線維芽細胞 / 癌関連線維芽細胞 / CAF / SASP |
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| Outline of Final Research Achievements |
This study focuses on the correlation between irradiation-induced cellular senescence in fibroblasts and tumor growth and epithelial-mesenchymal transition (EMT) in esophageal cancer cell lines through the effects of Senescence Associated Secretory Phenotype (SASP) by paracrine manner.
Irradiation to fibroblast cell line which was isolated from human esophageal cancer tissue induced the activation of fibroblasts as cancer-associated fibroblasts (CAFs). CAFs may be involved in tumor progression and epithelial-to-mesenchymal transition (EMT) through cell senescence and SASP enhancement.
Metformin, an anti-diabetes drug, can potentially ameliorate treatment resistance of esophageal cancer through the regulation of cellular senescence and SASP on CAFs.
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| Academic Significance and Societal Importance of the Research Achievements |
食道癌間質に存在する線維芽細胞における放射線誘導性細胞老化とそれに伴うSAPSは、腫瘍細胞の増殖や上皮間葉移行を促進するという観点で、腫瘍制御のための重要なターゲットとなりうることが証明された。
また、糖尿病治療薬として臨床応用における安全性が確認されているメトホルミンによる線維芽細胞株における細胞老化ならびにSASPの抑制作用は、食道癌の進展制御と線維化抑制、治療抵抗性改善のために有効な作用機序と考えられる。
同薬剤を用いた様々な難治性悪性腫瘍の治療抵抗性改善のための基礎的研究はこれまでになく、メトホルミンのDrug repositioningを利用した新規治療法の有効性が期待される。
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