Nicholas E Prevedel, Miles W Mee, Geoffrey A Wood, Brenda L Coomber
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引用次数: 0
摘要
犬淋巴瘤的标准治疗方法是 CHOP 化疗方案。蛋白酶体抑制剂已与 CHOP 一起用于人类血液恶性肿瘤的治疗,但在犬淋巴瘤的治疗中仍有待充分探索。我们在一组 15 名犬淋巴瘤患者中发现了对 CHOP 化疗反应差与蛋白酶体亚基 mRNA 表达水平高之间的关联,并试图确定蛋白酶体抑制剂对犬 B 细胞淋巴瘤细胞系(CLBL-1)活力的影响。这项研究的目的是调查蛋白酶体抑制剂是否会使这些细胞对CHOP药物多柔比星、长春新碱和环磷酰胺(4-羟基环磷酰胺/4-HC)敏感。CLBL-1 细胞对硼替佐米和伊沙佐米的蛋白酶体抑制作用敏感。硼替佐米的 IC50 为 15.1 nM,ixazomib 为 59.14 nM。蛋白酶体抑制剂加多柔比星对CLBL-1的存活率有协同作用;蛋白酶体抑制剂加长春新碱的作用因组合比例的不同而不同,加4-HC则有拮抗作用。这些结果可能具有临床实用性,因为蛋白酶体抑制剂有可能与增效的CHOP化合物一起使用,以提高犬淋巴瘤患者对化疗的反应性。
Effect of proteasome inhibitors on canine lymphoma cell response to CHOP chemotherapy in vitro.
The standard treatment for canine lymphoma is the CHOP chemotherapy regimen. Proteasome inhibitors have been employed with CHOP for the treatment of human haematological malignancies but remain to be fully explored in canine lymphoma. We identified an association between poor response to CHOP chemotherapy and high mRNA expression levels of proteasomal subunits in a cohort of 15 canine lymphoma patients, and sought to determine the effect of proteasome inhibitors on the viability of a canine B-cell lymphoma cell line (CLBL-1). The aim of this study was to investigate whether proteasome inhibitors sensitize these cells to the CHOP agents doxorubicin, vincristine and cyclophosphamide (as 4-hydroxycyclophosphamide/4-HC). CLBL-1 cells were sensitive to proteasome inhibition by bortezomib and ixazomib. The IC50 of bortezomib was 15.1 nM and of ixazomib was 59.14 nM. Proteasome inhibitors plus doxorubicin had a synergistic effect on CLBL-1 viability; proteosome inhibitors plus vincristine showed different effects depending on the combination ratio, and there was an antagonistic effect with 4-HC. These results may have clinical utility, as proteasome inhibition could potentially be used with a synergizing CHOP compound to improve responsiveness to chemotherapy for canine lymphoma patients.
期刊介绍:
Veterinary and Comparative Oncology (VCO) is an international, peer-reviewed journal integrating clinical and scientific information from a variety of related disciplines and from worldwide sources for all veterinary oncologists and cancer researchers concerned with aetiology, diagnosis and clinical course of cancer in domestic animals and its prevention. With the ultimate aim of diminishing suffering from cancer, the journal supports the transfer of knowledge in all aspects of veterinary oncology, from the application of new laboratory technology to cancer prevention, early detection, diagnosis and therapy. In addition to original articles, the journal publishes solicited editorials, review articles, commentary, correspondence and abstracts from the published literature. Accordingly, studies describing laboratory work performed exclusively in purpose-bred domestic animals (e.g. dogs, cats, horses) will not be considered.