Hypoxia inducible factor 1α expression and effects of its inhibitors in          canine lymphoma

Satoshi KAMBAYASHI; Masaya IGASE; Kosuke KOBAYASHI; Ayana KIMURA; Takako SHIMOKAWA MIYAMA; Kenji BABA; Shunsuke NOGUCHI; Takuya MIZUNO; Masaru OKUDA

doi:10.1292/jvms.15-0258

Internal Medicine

Hypoxia inducible factor 1α expression and effects of its inhibitors in canine lymphoma

Satoshi KAMBAYASHI, Masaya IGASE, Kosuke KOBAYASHI, Ayana KIMURA, Takako SHIMOKAWA MIYAMA, Kenji BABA, Shunsuke NOGUCHI, Takuya MIZUNO, Masaru OKUDA

Author information

Satoshi KAMBAYASHI
Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Masaya IGASE
Laboratory of Molecular Diagnosis and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Kosuke KOBAYASHI
Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Ayana KIMURA
Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Takako SHIMOKAWA MIYAMA
Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Kenji BABA
Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Shunsuke NOGUCHI
Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Laboratory of Molecular Diagnosis and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Takuya MIZUNO
Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Laboratory of Molecular Diagnosis and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Biomedical Science Center for Translational Research, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Masaru OKUDA
Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan
Biomedical Science Center for Translational Research, The United Graduate School of Veterinary Science, Yamaguchi University, 1677–1 Yoshida, Yamaguchi 753–8515, Japan

Keywords: canine lymphoma, echinomycin, HIF inhibitor, hypoxia inducible factor, xenograft model

JOURNAL FREE ACCESS

2015 Volume 77 Issue 11 Pages 1405-1412

DOI https://doi.org/10.1292/jvms.15-0258

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Abstract

Hypoxic conditions in various cancers are believed to relate with their malignancy, and hypoxia inducible factor-1α (HIF-1α) has been shown to be a major regulator of the response to low oxygen. In this study, we examined HIF-1α expression in canine lymphoma using cell lines and clinical samples and found that these cells expressed HIF-1α. Moreover, the HIF-1α inhibitors, echinomycin, YC-1 and 2-methoxyestradiol, suppressed the proliferation of canine lymphoma cell lines. In a xenograft model using NOD/scid mice, echinomycin treatment resulted in a dose-dependent regression of the tumor. Our results suggest that HIF-1α contributes to the proliferation and/or survival of canine lymphoma cells. Therefore, HIF-1α inhibitors may be potential agents to treat canine lymphoma.

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