2022 Fiscal Year Final Research Report
Exploring predictive factors to identify statin-sensitivity of cancer cells and building evidence for cancer metastasis inhibitors
| Project/Area Number |
19H03514
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
|---|
| Research Institution | Tottori University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
保坂 善真 九州大学, 農学研究院, 教授 (00337023)
太田 健一 香川大学, 医学部, 助教 (50403720)
|
|---|
| Project Period (FY) |
2019-04-01 – 2023-03-31
|
| Keywords | スタチン / がん細胞 / メバロン酸経路 / 細胞運動 / メタボローム |
|---|
| Outline of Final Research Achievements |
Statins are drugs used for hyperlipidemia and are expected to be used in cancer therapy from the viewpoint of drug repurposing (also termed drug repositioning). In this study, we used statin-sensitive and -resistant cancer cell lines to analyze (1) relationship between epithelial-mesenchymal transition (EMT) and statin sensitivity, (2) metabolic systems involved in statin sensitivity, and (3) effects on cell motility involved in cancer metastasis. As a result, EMT increased statin sensitivity of cancer cells. Also, statin-sensitive and -resistant cancer cell lines showed significantly different metabolic profiles after statin treatment, and these differences emerged as candidate factors related to statin sensitivity. The results also suggest that statins may exhibit anti-cancer effects in statin-sensitive cancer cells, even under hypoxic conditions, where drug resistance and invasive metastatic potential are enhanced.
|
| Free Research Field |
腫瘍生物学
|
| Academic Significance and Societal Importance of the Research Achievements |
スタチンの作用メカニズムを考えると、スタチンと他剤の併用で、がんの治療効果が上がることが予想される。しかしながら、それは、がん細胞がスタチンに対して感受性を示すのが前提であって、そもそもスタチンに感受性を示さないがん細胞では他剤との併用効果が望めない。本研究では、がん細胞の上皮間葉転換（EMT）とスタチン感受性との関連性を示し、また、スタチン処置したがん細胞の代謝物から情報を得て、スタチンの効果を増強させる可能性のある代謝系をスクリーニングした。候補に挙がった代謝系の阻害剤とスタチンを併用することにより、スタチンが効果を発揮するがんの種類や適用範囲を広げられるものと期待される。
|
