Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma.
Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho-extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma.
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Masanori
M
Masui
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tatsuo
T
Okui
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan shimotsu@md.okayama-u.ac.jp.
Tsuyoshi
T
Shimo
Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kiyofumi
K
Takabatake
Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
Takuya
T
Fukazawa
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kenichi
K
Matsumoto
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Naito
N
Kurio
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Soichiro
S
Ibaragi
Department of General Surgery, Kawasaki Medical School, Okayama, Japan.
Yoshio
Y
Naomoto
Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hitoshi
H
Nagatsuka
Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Akira
A
Sasaki
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000078792:Midkine; D009062:Mouth Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use*
C587597:3-(2-(4-fluorobenzyl)imidazo(2,1-beta)(1),(3)thiazol-6-yl)-2H-chromen-2-one; D000970:Antineoplastic Agents; D003374:Coumarins; D016207:Cytokines; D013844:Thiazoles; D000078792:Midkine
Midkine; angiogenesis; iMDK; oral squamous cell carcinoma