Potential clinical use of calpeptin for the treatment of MPM.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08633
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hyogo Medical University (2022-2023); Hyogo University of Health Sciences (2019-2021)
• Principal Investigator: Tabata Chiharu 兵庫医科大学, 薬学部, 教授 (90432393)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 中皮腫 / カルパイン / サイトカイン / 間質性肺炎 / 肺がん

Outline of Final Research Achievements

Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)1 and Tie2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang1induced proliferation of MPM cells through an NFkB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

現在、悪性中皮腫に対しては、世界的にもシスプラチン、ペメトレキセドと免疫チェックポイント阻害薬「オプジーボ（一般名：ニボルマブ）」以外の有効な抗がん剤に乏しく、また手術や放射線治療は治療抵抗性であるため、臨床上中皮腫の治療は非常に難渋している。そのため新規の抗がん剤の開発研究はわが国だけでなく世界的にも意義ある研究成果である。