Dékay Valéria, Karai Edina, Füredi András, Szebényi Kornélia, Szakács Gergely, Vajdovich Péter
Department of Clinical Pathology and Oncology, University of Veterinary Medicine Budapest, István Utca 2, H-1078 Budapest, Hungary.
Institute of Enzymology, Research Center of Natural Sciences, Eötvös Loránd Research Network, Magyar Tudósok Körútja 2, H-1117 Budapest, Hungary.
Cancers (Basel). 2022 Aug 13;14(16):3919. doi: 10.3390/cancers14163919.
Various mechanisms are known to be involved in the development of multidrug resistance during cancer treatment. P-glycoprotein (P-gp) decreases the intracellular concentrations of cytotoxic drugs by an energy-dependent efflux mechanism. The aim of this study was to investigate the predictive value of P-gp function based on the evaluation of P-gp activity in tumor cells obtained from canine B-cell lymphoma patients at diagnosis. P-gp function of 79 immunophenotyped canine lymphoma samples was determined by flow cytometry using the Calcein assay. Dogs were treated with either the CHOP or the L-CHOP protocol, a subset of relapsed patients received L-asparaginase and lomustine rescue treatments. Among the 79 dogs, the median overall survival time was 417 days, and the median relapse-free period was 301 days. 47 percent of the samples showed high P-gp activity, which was significantly higher in Stage IV cancer patients compared to Stage II + III and V. Whereas staging was associated with major differences in survival times, we found that the intrinsic P-gp activity of tumor cells measured at diagnosis is not predictive for therapy outcome. Further studies are needed to identify the intrinsic and acquired resistant mechanisms that shape therapy response and survival in B-cell canine lymphoma patients.
已知多种机制参与癌症治疗期间多药耐药性的发展。P-糖蛋白（P-gp）通过能量依赖的外排机制降低细胞毒性药物的细胞内浓度。本研究的目的是基于对犬B细胞淋巴瘤患者诊断时获得的肿瘤细胞中P-gp活性的评估，探讨P-gp功能的预测价值。使用钙黄绿素测定法通过流式细胞术测定79个免疫表型犬淋巴瘤样本的P-gp功能。犬只接受CHOP或L-CHOP方案治疗，一部分复发患者接受L-天冬酰胺酶和洛莫司汀挽救治疗。在这79只犬中，中位总生存时间为417天，中位无复发生存期为301天。47%的样本显示P-gp活性高，IV期癌症患者的P-gp活性显著高于II + III期和V期患者。虽然分期与生存时间的主要差异相关，但我们发现诊断时测量的肿瘤细胞固有P-gp活性不能预测治疗结果。需要进一步研究以确定影响B细胞犬淋巴瘤患者治疗反应和生存的固有和获得性耐药机制。
