Elucidation of the anti-cancer mechanism of statins and development of a new evaluation method to predict their anti-tumor effect

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18439
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnostics
• Research Institution: Tottori University
• Principal Investigator: WARITA Katsuhiko 鳥取大学, 農学部, 准教授 (40452669)
• Research Collaborator: ISHIKAWA takuro ; HOSAKA yoshinao ; Oltvai zoltan n. ; Wells alan
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: スタチン / がん細胞 / 化学療法 / 薬効評価と予測 / 制がん効果

Outline of Final Research Achievements

In recent years, the anti-tumor effect of statins, drugs used for hyperlipidemia, has become the focus of attention. Statins are reported to be effective against mesenchymal cancer cells; however, the molecular mechanism underlying the effect of statins on these cells remains unclear. In this study, differences in dependence on the mevalonate pathway, the route of endogenous cholesterol synthesis that is inhibited by statins, were compared between statin-sensitive cell lines (mesenchymal cancer cells) and statin-resistant cell lines (epithelial cancer cells). Results showed that mesenchymal cancer cells were more dependent on the mevalonate pathway than epithelial cancer cells; moreover, statin sensitivity significantly increased when expression of the statin-target molecule was suppressed with siRNA, even in epithelial cancer cells.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

スタチンは血中コレステロールの低下薬としてすでに実績のある薬剤であり、従来の抗がん剤と違い副作用が少なく、また、副作用のデータ蓄積も豊富であるため、がん治療への臨床応用までに長い時間と膨大な費用を要しないのが利点である。本研究を通して、スタチン耐性を示す上皮系がん細胞にスタチン感受性を付加・増強する方法が明らかとなってきた。本研究で得られた成果を発展させれば、転移する前の上皮系がん細胞にもスタチンが制がん効果を発揮し、がんの治療成績の向上が望めると考えている。