Pawlak Aleksandra, DE Miguel Diego, Kutkowska Justyna, Obmińska-Mrukowicz Bożena, Rapak Andrzej, Martinez-Lostao Luis
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wroclaw, Poland
Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
Anticancer Res. 2017 Dec;37(12):6655-6665. doi: 10.21873/anticanres.12123.
BACKGROUND/AIM: Targeting the extrinsic apoptotic pathway is an interesting option for anticancer therapy. A protein which such ability is Apo2 ligand, also known as TNF-related apoptosis-inducing ligand (TRAIL). The aim of this study was to examine the possibility of sensitizing resistant CLBL-1 canine lymphoma cells to TRAIL-induced apoptosis by using flavopiridol (FVP) a cyclin-dependent kinase inhibitor (CDKs).
The CLBL-1 (canine B-cell lymphoma cell line) was used in the study. The effect of FVP and TRAIL treatment on apoptosis induction was assessed by flow cytometry and western blot.
Although canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cells.
Our results demonstrated that although canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cell line. Although further investigation is required to deepen the knowledge of TRAIL as an antitumor agent in canine cancers, our results open the door to future use of TRAIL-based treatment strategies in veterinary oncology.
背景/目的：靶向细胞外凋亡途径是抗癌治疗的一个有趣选择。具有这种能力的一种蛋白质是Apo2配体，也称为肿瘤坏死因子相关凋亡诱导配体（TRAIL）。本研究的目的是通过使用细胞周期蛋白依赖性激酶抑制剂（CDK）黄酮哌啶醇（FVP）来检测使耐药的CLBL-1犬淋巴瘤细胞对TRAIL诱导的凋亡敏感的可能性。
本研究使用CLBL-1（犬B细胞淋巴瘤细胞系）。通过流式细胞术和蛋白质印迹法评估FVP和TRAIL处理对凋亡诱导的影响。
尽管犬淋巴瘤细胞对TRAIL诱导的凋亡具有抗性，但这种死亡配体与FVP的联合能够克服CLBL-1淋巴瘤细胞的TRAIL抗性。
我们的结果表明，尽管犬淋巴瘤细胞对TRAIL诱导的凋亡具有抗性，但这种死亡配体与FVP的联合能够克服CLBL-1淋巴瘤细胞系的TRAIL抗性。尽管需要进一步研究以加深对TRAIL作为犬癌症抗肿瘤药物的认识，但我们的结果为未来在兽医肿瘤学中使用基于TRAIL的治疗策略打开了大门。
