Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma.
Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma.
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发表时间：
2016-06
影响因子：
2
通讯作者：
M. Masui;T. Okui;T. Shimo;Kiyofumi Takabatake;T. Fukazawa;Kenichi Matsumoto;N. Kurio;S. Ibaragi;Y. Naomoto;H. Nagatsuka;A. Sasaki
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作者：
M. Masui;T. Okui;T. Shimo;Kiyofumi Takabatake;T. Fukazawa;Kenichi Matsumoto;N. Kurio;S. Ibaragi;Y. Naomoto;H. Nagatsuka;A. Sasaki
中期因子是一种肝素结合生长因子，在多种人类恶性肿瘤中高度表达。然而，其在口腔鳞状细胞癌生长中的作用尚不清楚。在这项研究中，我们分析了一种新的中期因子抑制剂（iMDK）对口腔鳞状细胞癌的抗肿瘤作用。在口腔鳞状细胞癌HSC-2细胞和SAS细胞异种移植模型中，iMDK的给药诱导了稳健的抗肿瘤反应并抑制了分化簇31（CD 31）的表达。iMDK剂量依赖性地抑制这些细胞的增殖，以及HSC-2和SAS细胞中中期因子和磷酸化细胞外信号调节激酶的表达。此外，iMDK显着抑制血管内皮生长因子和诱导人脐静脉内皮细胞的管生长的剂量依赖性的方式。这些结果表明，中期因子是关键参与口腔鳞状细胞癌和iMDK可以有效地用于治疗口腔鳞状细胞癌。
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.