Classification based on oncometabolites of cancers for which statins are used and analysis of the effects of statins in tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07666
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kwansei Gakuin University
• Principal Investigator: Warita Tomoko 関西学院大学, 生命環境学部, 講師 (00753112)
• Co-Investigator(Kenkyū-buntansha): 大谷 清 関西学院大学, 生命環境学部, 教授 (30201974) ; 割田 克彦 鳥取大学, 農学部, 教授 (40452669)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: スタチン系薬剤 / がん細胞 / ドラッグリポジショニング / スタチン感受性 / HMGCR

Outline of Final Research Achievements

We examined the cell characteristics of cancers for which statins are effective antitumor agents. Expression of HMGCS1, which synthesizes HMG-CoA, was higher in statin-resistant cancer cells than in statin-sensitive cancer cells; however, it did not profoundly alter statin-resistant or statin-sensitive cancer cells after statin treatment. Expression of HMGCR, whose substrate is HMG-CoA, was significantly increased by statin treatment in both statin-resistant and statin-sensitive cancer cells, and induction of HMGCR degradation augmented the anticancer effects of statins. Additionally, statins have been suggested to make cancer cells vulnerable to oxidative stress. This study suggests that in statin-resistant cancer cells, high HMGCS1 expression maintains intracellular HMG-CoA levels, counteracting HMGCR inhibition by statins; statin-resistant cancer cells may also respond to oxidative stress using more sophisticated mechanisms.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

スタチンは、脂質異常症の治療薬として実績のある既存薬であり、副作用のデータも蓄積されていることから、ドラッグリポジショニングによるがん治療への応用が期待できる薬剤である。しかし、スタチンはすべてのがんに制がん効果を発揮するわけではなく、スタチンが奏効するがんを診断するための細胞特性の同定が必須である。本研究では、臨床応用に繋げていくために、がんにおけるスタチン適用範囲を拡げるべく、がん細胞のスタチン感受性の増強を試みたことに意義がある。