Analysis of antitumor effects of adiponectin receptor agonists on pancreatic cancer
| Project/Area Number |
16K21177
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
General pharmacology
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| Research Institution | Teikyo University (2017-2019)
Shimane University (2016) |
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Principal Investigator |
Akimoto Miho 帝京大学, 医学部, 助教 (60437556)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | AdipoRon / 膵がん / ネクロトーシス / 抗腫瘍効果 / アディポネクチン / ネクロプトーシス / 腫瘍血管形成 / 経口投与 / 細胞死 / ROS / カルシウム / アディポネクチン受容体アゴニスト / アポトーシス |
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| Outline of Final Research Achievements |
In this study, we found that adiponectin receptor agonist AdipoRon induces cell death in pancreatic cancer cells and clarified the molecular mechanism. In pancreatic cancer cells, AdipoRon activates ERK1/2 via adiponectin receptor AdipoR1, followed by accumulation of calcium and increased production of superoxide in mitochondria, to induce necroptosis by inducing mitochondrial dysfunction. In addition, AdipoRon suppressed tumor growth without serious side effects by oral administration to pancreatic cancer-bearing mice, and showed a cell killing effect on cancer cells derived from patients with pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、AdipoRonがヒト膵がん細胞の細胞死を誘導する分子機序を明らかにするとともに、動物実験や膵がんの臨床検体を用いたアッセイでもAdipoRonが膵がんに対する抗腫瘍効果を示すことを明らかにした。AdipoRonは抗糖尿病薬としての臨床応用が期待されているが、これまでがん治療への応用は試みられていない。本研究により得られた新たな知見は、アディポネクチン受容体アゴニストを膵がん治療に応用するための科学的な根拠となりうる。
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Report
(5 results)
Research Products
(21 results)
