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Inhibition of angiogenesis and tumor progression of MK-0429, an integrin αvß3 antagonist, on oral squamous cell carcinoma.
Nakagawa, Takayuki; Ohta, Kouji; Naruse, Takako; Sakuma, Miyuki; Fukada, Syohei; Yamakado, Nao; Akagi, Misaki; Sasaki, Kazuki; Niwata, Chieko; Ono, Shigehiro; Aikawa, Tomonao.
Afiliação
  • Nakagawa T; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan. tnakaga@hiroshima-u.ac.jp.
  • Ohta K; Department of Public Oral Health, Program of Oral Health Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Naruse T; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Sakuma M; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Fukada S; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Yamakado N; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Akagi M; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Sasaki K; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Niwata C; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Ono S; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
  • Aikawa T; Department of Oral and Maxillofacial Surgery, Program of Dentistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ward, Hiroshima, 734-8553, Japan.
J Cancer Res Clin Oncol ; 148(12): 3281-3292, 2022 Dec.
Article em En | MEDLINE | ID: mdl-35713706
ABSTRACT

PURPOSE:

Integrin αvß3 is an essential molecule for tumor angiogenesis. This study aimed to investigate the anti-tumor effect of MK-0429, an integrin αvß3 antagonist, on oral squamous cell carcinoma (OSCC) through its inhibitory effect on angiogenesis.

METHODS:

In this study, we investigated the effect of MK-0429 on cellular function and angiogenesis in vitro with the use of an immortalized human umbilical vein endothelial cell, HUEhT-1, which is immortalized by the electroporatic transfection of hTERT. The effect of MK-0429 on the integrin αvß3 signaling pathway was examined by FAK, MEK1/2 and ERK 1/2 phosphorylation. The anti-angiogenic effect of MK-0429 was evaluated by in vitro tube formation assay. The anti-tumor effect on OSCC was assessed by administrating MK-0429 to mouse oral cancer xenografts.

RESULTS:

MK-0429 inhibited cell proliferation, migration, and adhesion of HUEhT-1 in a dose-dependent manner. FAK, MEK and ERK phosphorylation were significantly blocked by MK-0429 treatment. Tube formation was suppressed by MK-0429 in dose-dependent manner. Tumor progression was significantly suppressed by MK-0429 administration in mouse oral cancer xenografts. Histological study revealed that MK-0429 decreased tumor vascularization.

CONCLUSION:

These results indicated integrin αvß3 as a therapeutic target for OSCC and suggested that MK-0429 might be clinically applicable as an anti-tumor agent with potent anti-angiogenic activity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Bucais / Carcinoma de Células Escamosas / Neoplasias de Cabeça e Pescoço Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Bucais / Carcinoma de Células Escamosas / Neoplasias de Cabeça e Pescoço Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article