Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan.
Laboratory of Veterinary Surgery, Faculty of Agricultural and Life Sciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Res Vet Sci. 2020 Oct;132:466-473. doi: 10.1016/j.rvsc.2020.08.007. Epub 2020 Aug 8.
Recombinant canine interferon-γ (rc-IFNγ; Interdog) was exclusively approved as a therapeutic for canine atopic dermatitis. However, it has been used off-label for the treatment of canine cancer. We examined the inhibitory effect of rc-IFNγ on the growth of canine tumor cell lines and analyzed its mechanism of action. Three (CTB-p, CTB-m, and CNM-m) out of seven mammary gland tumor cell lines and two (VIMC and CoMS) out of four mast cell tumor cell lines showed remarkable growth inhibition after treatment with rc-IFNγ. However, one (CLBL-1) out of nine lymphoma cell lines showed a significant amount of cell death. Using CTB-p and CTB-m cell lines, we showed that STAT1 was essential for inducing the growth inhibitory effect of rc-IFNγ. Although rc-IFNγ induced G1 growth arrest in CTB-p cell line, treatment with rc-IFNγ did not alter the expression of cell cycle regulatory proteins. In this study, we observed direct cytotoxicity or cytostatic effects of rc-IFNγ in canine tumor cell lines. However, the detailed mechanisms responsible for these effects need to be elucidated in the future.
重组犬干扰素-γ(rc-IFNγ;Interdog)仅被批准作为犬特应性皮炎的治疗药物。然而,它已被超适应证用于治疗犬癌症。我们研究了 rc-IFNγ对犬肿瘤细胞系生长的抑制作用,并分析了其作用机制。在七种乳腺肿瘤细胞系中,有三种(CTB-p、CTB-m 和 CNM-m)和四种肥大细胞瘤细胞系中的两种(VIMC 和 CoMS)在经过 rc-IFNγ处理后表现出明显的生长抑制。然而,在九个淋巴瘤细胞系中有一种(CLBL-1)表现出大量的细胞死亡。使用 CTB-p 和 CTB-m 细胞系,我们表明 STAT1 对于诱导 rc-IFNγ的生长抑制作用是必需的。尽管 rc-IFNγ在 CTB-p 细胞系中诱导了 G1 期生长停滞,但 rc-IFNγ处理并未改变细胞周期调节蛋白的表达。在本研究中,我们观察到 rc-IFNγ对犬肿瘤细胞系具有直接的细胞毒性或细胞抑制作用。然而,这些作用的详细机制需要在未来阐明。