黄酮哌啶醇强烈增强犬淋巴瘤细胞对TRAIL诱导凋亡的敏感性。

Flavopiridol Strongly Sensitizes Canine Lymphoma Cells to TRAIL-induced Apoptosis.

作者信息

Pawlak Aleksandra, DE Miguel Diego, Kutkowska Justyna, Obmińska-Mrukowicz Bożena, Rapak Andrzej, Martinez-Lostao Luis

机构信息

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.

出版信息

Anticancer Res. 2017 Dec;37(12):6655-6665. doi: 10.21873/anticanres.12123.

DOI:10.21873/anticanres.12123

PMID:29187441

Abstract

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).

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

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。