| Project/Area Number |
18K08678
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 55020:Digestive surgery-related
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 進行再発大腸癌 / 抗がん剤耐性 / COX-2阻害剤 / 癌幹細胞 / 大腸癌 / 化学療法耐性 / バイオマーカー / 大腸癌治療抵抗性 / 直腸癌 / 術前化学療法 / 癌幹細胞仮説 |
|---|
| Outline of Final Research Achievements |
As a result of comprehensive analysis of gene expression by suppressing Syntenin-1 using colorectal cancer cell lines SW480, SW620, and HT29, changes in prostaglandin signal were observed. This was the same as the behavior when COX2 was inhibited. This suggests that Syntenin-1 is involved in the COX-2 signal. LGR5 is said to control stem cell nature, but inhibition of Syntenin-1 reduced anticancer drug resistance to support this stem cell nature. When used in combination with a COX-2 inhibitor to increase the sensitivity of chemotherapy, a significant synergistic effect was observed. The possibility as a useful combination therapy was suggested.
|
| Academic Significance and Societal Importance of the Research Achievements |
癌幹細胞表面分子である全長型LGR5、LGR5スプライシングバリアントの意義を解明すべく遺伝子ではなく、タンパク質の網羅的解析を行った。結果Syntenin-1が同定された。Syntenin-1はCOX-2シグナルの伝達に重要な役割を果たしており抗がん剤耐性に寄与した。
この事実を臨床応用するに際し、現在施行されている化学療法の感受性を増強させるためにCOX-2阻害剤との併用を行ったところ、著明な相乗効果を認めた。現状の化学療法もCOX-2阻害剤も臨床応用が可能なため、COX-2阻害剤が抗がん剤としてのドラッグリポジショニングとしての可能性が示唆された。
|
