Developmental study of oral cancer treatment using vitamin D derivative (ED-71) which is used for an osteoporosis treatment

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K11723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Shintani Tomoaki 広島大学, 病院(歯), 助教 (90403518)
• Co-Investigator(Kenkyū-buntansha): 岡本 哲治 広島大学, 医歯薬保健学研究科(歯), 教授 (00169153) ; 林堂 安貴 広島大学, 病院(歯), 講師 (70243251)
• Research Collaborator: Usui Emiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: HBp17/FGFBP-1 / ビタミンD3

Outline of Final Research Achievements

In this study, we examined the potential anti-tumor effect of ED-71, an analog of 1α,25(OH)2D3, for squamous cell carcinoma cells in vitro and in vivo.The cell lines used were oral squamous cell carcinoma cell lines (NA and UE) established from oral cancer patients, and an epidermoid carcinoma(A431). The growth assay in serum-free culture revealed that ED-71 inhibited the growth of the cancer cell lines in a dose-dependent manner.Oral administration of ED-71 significantly inhibited the growth of A431-derived tumors in athymic nude mice. Immunohistochemical analysis revealed that the expression of HBp17/FGF-BP1, FGF-2, CD31, and Ki-67 in the tumors of ED71-treated group was down-regulated in comparison to control.
These results suggest that ED-71 possesses potential anti-tumor activity for SCCs both in vitro and in vivo. This compound may act directly on the tumor cells or on endothelial cells by modulating the tumor microenvironment.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

1α,25(OH)2D3の異性体であるED-71は現在、商品名エディロールとして骨粗鬆症の治療薬として使用されている。我々は、ED-71が、転写因子NF-κBシグナル伝達経路を抑制することにより，SCC/OSCC細胞のHBp17/FGFBP 発現が抑制されることを明らかにした。ED-71は口腔扁平上皮癌細胞に対して増殖抑制効果を示し、さらに血管新生抑制を介して抗腫瘍活性を示すことが明らかとなり、ED-71を用いた口腔扁平上皮癌治療の有用性が考えられた。