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  3. Enhancement of radio-sensitivity by inhibition of Janus kinase signaling with oclacitinib in canine tumor cell lines

Enhancement of radio-sensitivity by inhibition of Janus kinase signaling with oclacitinib in canine tumor cell lines

  • Mol Ther Oncol. 2025 Feb 3;33(1):200946. doi: 10.1016/j.omton.2025.200946.
Ryo Owaki 1,  Kenji Hosoya 2,  Tatsuya Deguchi 2,  Satoru Konnai 3 4,  Naoya Maekawa 3,  Tomohiro Okagawa 3,  Hironobu Yasui 5,  Sangho Kim 1,  Takafumi Sunaga 1,  Masahiro Okumura 1
Affiliations

Affiliations

  • 1 Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • 2 Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • 3 Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • 4 Laboratory of Infectious Diseases, Department of Disease Control, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
  • 5 Laboratory of Radiation Biology, Department of Applied Veterinary Science, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
PMID: 40051504 DOI: 10.1016/j.omton.2025.200946
Abstract

A combination of irradiation and oclacitinib, a Janus kinase (JAK) inhibitor used in dogs, could lead to synergistic Anticancer effects in canine tumors. However, the anti-tumor effects of oclacitinib remain unclear. This study investigated the radio-sensitizing effect of oclacitinib in canine tumors and determined its underlying mechanisms using osteosarcoma (HMPOS), malignant melanoma (CMeC), and thyroid adenocarcinoma (CTAC) cell lines. A clonogenic assay and a tumor growth assessment in a xenograft mouse model (BALB/cAJcl-nu/nu) were performed to evaluate the radio-sensitizing effects of oclacitinib. Oclacitinib enhanced the radio-sensitivity of tumor cells both in vitro and in vivo. The signal transducer and activator of transcription (STAT)3 expression was activated and suppressed by oclacitinib in X-irradiation-exposed cells. Oclacitinib enhanced radiation-induced Apoptosis only in HMPOS cells by inhibiting anti-apoptotic genes. In addition, oclacitinib inhibited the transcription of cell-cycle-regulating genes and arrested cell cycle progression from the G1 phase to subsequent phases. In conclusion, oclacitinib enhanced radio-sensitivity both in vitro and in vivo by triggering Apoptosis and impeding cell cycle progression via STAT3 inhibition in canine tumor cell lines. This study suggested the clinical therapeutic potential of oclacitinib and radiation therapy in enhancing treatment efficacy and outcomes in canine tumors.

Keywords

JAK inhibitor; dog; oncology; radiation; signaling pathway.

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