Effects of peritumoral bevacizumab injection against oral squamous cell carcinoma in a nude mouse xenograft model: A preliminary study

Yoshida,Hisato; Yoshimura,Hitoshi; Matsuda,Shinpei; Ryoke,Takashi; Kiyoshima,Tamotsu; Kobayashi,Motohiro; Sano,Kazuo

doi:10.3892/ol.2018.8399

Effects of peritumoral bevacizumab injection against oral squamous cell carcinoma in a nude mouse xenograft model: A preliminary study

Authors:
- Hisato Yoshida
- Hitoshi Yoshimura
- Shinpei Matsuda
- Takashi Ryoke
- Tamotsu Kiyoshima
- Motohiro Kobayashi
- Kazuo Sano
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Affiliations: Department of Dentistry and Oral Surgery, Unit of Sensory and Locomotor Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910‑1193, Japan, Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka 812‑8582, Japan, Department of Tumor Pathology, Unit of Pathological Sciences, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui 910‑1193, Japan
Published online on: March 30, 2018 https://doi.org/10.3892/ol.2018.8399
Pages: 8627-8634
Copyright: © Yoshida et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angiogenesis serves a crucial role in tumor growth. Vascular endothelial growth factor (VEGF) is a potent regulator of tumor angiogenesis and is highly expressed in oral squamous cell carcinoma (OSCC). Bevacizumab, which binds to VEGF‑A, inhibits the biological activity of VEGF and is clinically administered by intravenous injection. As intravenous chemotherapy intensifies the side effects experienced by OSCC patients, an alternative treatment option is desirable, particularly for older patients with OSCC who present with systemic disease complications. Generally, local injections of antitumor agents enhance tumoricidal activity and decrease side effects. However, the antitumor effects of peritumoral bevacizumab injections in OSCC are not fully understood. Therefore, the present study examined the effects of peritumoral bevacizumab injections in an experimental nude mouse model of OSCC through immunohistochemical staining for cluster of differentiation (CD)31 and α‑smooth muscle actin (α‑SMA) and apoptosis assays. It was identified that peritumoral injections of bevacizumab significantly inhibited tumor growth in OSCC xenografts compared with peritumoral saline injections or no treatment (controls), and it was also revealed that treatment with bevacizumab significantly reduced CD31‑ and α‑SMA‑positive microvessel density (P<0.01) and increased level of tumor cell apoptosis (P<0.01) compared with the controls. In conclusion, these results collectively support the experimental basis for the clinical development of peritumoral bevacizumab injections for the treatment of OSCC.

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