Establishment of a novel treatment with ivermectin targeting the Hippo pathway to gastric cancer.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07177
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Kyushu University
• Principal Investigator: Eguchi Hidetoshi 九州大学, 大学病院, 講師 (90527756)
• Co-Investigator(Renkei-kenkyūsha): MIMORI KOSHI
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胃癌 / Hippo経路 / YAP1 / イベルメクチン / リポジショニングドラッグ / 数理統計解析

Outline of Final Research Achievements

We aimed to clarify whether ivermectin, an antiparasitic drug, had antitumor effects on gastric cancer (GC) through inhibition of YAP1. In GC cell xenografts, ivermectin suppressed tumor growth.we explored the mechanism through which ivermectin regulated YAP1 expression. Ivermectin inhibited YAP1 nuclear expression and the downstream gene CTGF expression in GC cells. Ivermectin decreased YAP1 mRNA expression, thereby inhibiting nuclear accumulation of YAP1 in MKN1 cells. In survival analysis, low YAP1 mRNA expression was associated with a better prognosis in three independent GC datasets.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

スキルス胃癌は比極めて予後の悪い腫瘍であり、腹膜播種の機序については未知な部分が多く、有効な治療法の確立が待たれる。我々はイベルメクチンがHippo経路の転写因子であるYAP1の 阻害効果を有することを見出し、 同薬剤投与により腹膜播種の抑制効果が期待される。またイベルメクチンはリポジショニングドラッグとしても有用性が期待される。