Studies for clinical application of PDE1 inhibitors to the treatment of malignant melanoma

• Project/Area Number: 18K09765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Mie University
• Principal Investigator: Shimizu Kasumi 三重大学, 医学部附属病院, 講師 (20378368)
• Co-Investigator(Kenkyū-buntansha): 村田 琢 三重大学, 医学部附属病院, 講師 (80242965)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: phosphodiesterase / 悪性腫瘍

Outline of Final Research Achievements

As a result of confirming the expression of PDE in the highly metastatic malignant melanoma cell line A375SM used in the experiment, the expression of PDE1 activity and PDE1C mRNA was confirmed. In addition, the expression of PDE5A was slight, consistent with the characteristics of PDE expression of MAA.
Pulmonary metastasis was confirmed by transplanting A375SM cells from the orbital venous plexus, but it was thought that sufficient effects could not be expected by the method of allowing cells to act with a PDE1 inhibitor and then transplanting to mice, so inhibition after transplanting A375SM cells. We decided to perform the experiment by intraperitoneally administering the drug and comparing the lung metastases with the control group. However, further studies are needed on the optimal concentration of sildenafil to confirm the PDE1 inhibitory effect.

Academic Significance and Societal Importance of the Research Achievements

悪性黒色腫は、さまざまな治療に抵抗性で、かつ極めて悪性度が高いことで知られ、新治療法の開発が急務である。本研究によって、高転移悪性黒色腫細胞株にもPDE1が発現していることが確認され、PDE1阻害剤が悪性黒色腫細胞の治療に応用できる可能性が高くなった。