Identification of new therapy for HCC based on stemness surface markers

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: OISHI NAOKI 金沢大学, 医学系, 協力研究員 (20507040)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 肝細胞癌 / 上皮間葉系移行 / ヒストン修飾タンパク阻害薬 / DNAメチル化制御タンパク阻害薬 / 癌幹細胞

Outline of Final Research Achievements

I evaluated the relationship between epithelium-Mesenchymal transition and features of hepatic cancer stem cells. Moreover, I identified new therapy based on a pattern of stemness surface markers. In epithelial-like HCC cases, highly expression of EpCAM or CD133, or activation of HDAC1 pathway indicated poor prognosis. While, in mesenchymal-like HCC cases, highly expression of CD56 or CD90, or activation of DNMT1 or DNMT3b pathways were poor prognostic marker. HDAC1 inhibitor suppressed tumor proliferation and invasion in Epithelial-like HCC cells. On the other hand, DNMT inhibitor showed the anti-tumor effect in Mesenchymal-like HCC cells. In Epithelial-like HCC cells, combination DNA-effected anti-cancer drugs and HDAC inhibitor indicated synergistic effect in the suppression of tumor proliferation and invasion. This combination therapy may be new therapy for Epithelial-like HCC cases.

Free Research Field

肝臓病学