Pawlak Aleksandra, Kutkowska Justyna, Obmińska-Mrukowicz Bożena, Rapak Andrzej
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, C.K. Norwida 31, 50-375 Wroclaw, Poland.
Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Weigla 12, 53-114 Wroclaw, Poland.
Res Vet Sci. 2017 Oct;114:518-523. doi: 10.1016/j.rvsc.2017.09.026. Epub 2017 Sep 28.
Methotrexate is an antimetabolite used in the treatment of cancer and non-malignant diseases including rheumatoid arthritis, psoriasis and graft vs. host disease. Combination therapy with methotrexate was successful in the treatment of canine lymphoma, mammary tumor and invasive urinary bladder cancer. Lymphoma, the most common hematopoietic cancer in dogs, and leukemia are sensitive to chemotherapy, which is why methotrexate may be an important treatment option for these diseases. Although methotrexate is already used in veterinary oncology its effects on canine cancer cells has not been tested. The aim of the study was to evaluate for the first time methotrexate concentration-dependent cytotoxicity and its capability of inducing apoptosis in selected canine lymphoma/leukemia cell lines: CLBL-1, GL-1 and CL-1 as a first step before the in vitro development of new therapeutic options with the use of methotrexate.
Methotrexate exhibited concentration-dependent inhibitory effect on proliferation of all the examined cell lines with different degree of apoptosis induction. The most methotrexate sensitive cells belonged to CL-1 cell line derived from T cell neoplasia and previously characterized by high resistance to the majority of anticancer drugs used in the therapy of lymphoma/leukemia in dogs. Canine lymphoma and leukemia cell lines are sensitive to methotrexate, and this drug may be useful in effective treatment of canine neoplasms and especially of T-type leukemia/lymphoma.
甲氨蝶呤是一种抗代谢药物，用于治疗癌症和非恶性疾病，包括类风湿性关节炎、牛皮癣和移植物抗宿主病。甲氨蝶呤联合疗法成功用于治疗犬淋巴瘤、乳腺肿瘤和浸润性膀胱癌。淋巴瘤是犬类最常见的造血系统癌症，白血病对化疗敏感，这就是为什么甲氨蝶呤可能是这些疾病的重要治疗选择。尽管甲氨蝶呤已用于兽医肿瘤学，但其对犬癌细胞的作用尚未得到测试。本研究的目的是首次评估甲氨蝶呤在选定的犬淋巴瘤/白血病细胞系（CLBL-1、GL-1和CL-1）中的浓度依赖性细胞毒性及其诱导凋亡的能力，这是在体外开发使用甲氨蝶呤的新治疗方案之前的第一步。
甲氨蝶呤对所有检测的细胞系增殖均表现出浓度依赖性抑制作用，并诱导不同程度的凋亡。对甲氨蝶呤最敏感的细胞属于CL-1细胞系，该细胞系源自T细胞肿瘤，此前其特点是对犬淋巴瘤/白血病治疗中使用的大多数抗癌药物具有高抗性。犬淋巴瘤和白血病细胞系对甲氨蝶呤敏感，这种药物可能有助于有效治疗犬类肿瘤，尤其是T型白血病/淋巴瘤。
