The therapeutic role of DPP-4 inhibitor for the progression of Hepatocellular carcinoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19374
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kawasaki Medical School
• Principal Investigator: Nishina Sohji 川崎医科大学, 医学部, 講師 (70550961)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 肝細胞癌 / DPP4阻害剤 / CXCL10 / NK細胞 / 走化性

Outline of Final Research Achievements

Anagliptin significantly suppressed the growth of nude mice xenograft tumors (HCC) in vivo. Anagliptin also induced NK cells infiltrations to necrotic lesion in tumor more vigorously. The reduction in growth of xenograft tumor by anagliptin was completely canceled by depleting NK cells with anti-CXCR3 antibody or anti-ASGM1. Anagliptin significantly enhanced the mobility of NK cells in the presence of CXCL10. CXCL10(1-77aa) is truncated at its N-terminus through DPP-4 activity and a N-terminal truncated CXCL10(3-77aa) acts as chemokine antagonist. We quantified the concentration of intact CXCL10 and truncated CXCL10. DPP4 inhibitors almost completely suppressed CXCL10 to be truncated, indicating that NK cell trafficking is enhanced through the prevention of CXCL10 from being truncated by DPP4 inhibitors.
Thus, DPP-4 inhibitor suppressed HCC progression through activation of NK cell chemotaxis.

Free Research Field

肝臓