Cheng Nan, Diao Hongxiu, Lin Zhaoyan, Gao Jiafeng, Zhao Ying, Zhang Weijiao, Wang Qi, Lin Jiahao, Zhang Di, Jin Yipeng, Bao Yongping, Lin Degui
Department of Veterinary Clinical Science, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Faculty of Medicine and Health, Norwich Medical School, University of East Anglia, Norwich, United Kingdom.
Front Vet Sci. 2020 Nov 11;7:580530. doi: 10.3389/fvets.2020.580530. eCollection 2020.
Canine mammary carcinoma is common in female dogs, and its poor prognosis remains a serious clinical challenge, especially in developing countries. Benzyl isothiocyanate (BITC) has attracted great interest because of its inhibitory effect against tumor activity. However, its effect and the underlying mechanisms of action in canine mammary cancer are not well-understood. Here, we show that BITC suppresses mammary tumor growth, both and , and reveal some of the potential mechanisms involved. The effect of BITC on canine mammary cancer was evaluated on CIPp and CMT-7364, canine mammary carcinoma lines. The cell lines were treated with BITC and then subjected to wound healing and invasion assays. Cell cycles and apoptosis were measured using flow cytometry; TUNEL assay; immunohistochemistry (IHC) for caspase 3, caspase 9, and cyclin D1; hematoxylin and eosin (H&E) staining; and/or quantitative polymerase chain reaction (qPCR). BITC showed a strong suppressive effect in both CIPp and CMT-7364 cells by inhibiting cell growth ; these effects were both dose- and time-dependent. BITC also inhibited migration and invasion of CIPp and CMT-7364 cells. BITC induced G2 arrest and apoptosis, decreasing tumor growth in nude mice by downregulation of cyclin B1 and Cdk1 expression. BITC suppressed both invasion and migration of CIPp and CMT-7364 cells and induced apoptosis. BITC inhibited canine mammary tumor growth by suppressing cyclinB1 and Cdk1 expression in nude mice.
犬乳腺癌在雌性犬中很常见，其预后较差仍然是一个严峻的临床挑战，尤其是在发展中国家。异硫氰酸苄酯（BITC）因其对肿瘤活性的抑制作用而备受关注。然而，其在犬乳腺癌中的作用效果及潜在作用机制尚不清楚。在此，我们表明BITC可抑制乳腺肿瘤生长，并揭示了一些潜在的相关机制。在犬乳腺癌细胞系CIPp和CMT-7364上评估了BITC对犬乳腺癌的作用。用BITC处理细胞系，然后进行伤口愈合和侵袭实验。使用流式细胞术、TUNEL检测、caspase 3、caspase 9和细胞周期蛋白D1的免疫组织化学（IHC）、苏木精和伊红（H&E）染色以及/或定量聚合酶链反应（qPCR）来测量细胞周期和凋亡。BITC通过抑制细胞生长在CIPp和CMT-7364细胞中均显示出强大的抑制作用；这些作用呈剂量和时间依赖性。BITC还抑制了CIPp和CMT-7364细胞的迁移和侵袭。BITC诱导G2期阻滞和凋亡，通过下调细胞周期蛋白B1和Cdk1的表达减少裸鼠体内肿瘤生长。BITC抑制了CIPp和CMT-7364细胞的侵袭和迁移并诱导凋亡。BITC通过抑制裸鼠体内细胞周期蛋白B1和Cdk1的表达来抑制犬乳腺肿瘤生长。
