热休克蛋白70（Hsp70）抑制剂VER155008可诱导间变性甲状腺癌细胞发生副凋亡，此过程需要从头合成蛋白质。
The hsp70 inhibitor VER155008 induces paraptosis requiring de novo protein synthesis in anaplastic thyroid carcinoma cells.
作者信息
Kim Si Hyoung, Kang Jun Goo, Kim Chul Sik, Ihm Sung-Hee, Choi Moon Gi, Yoo Hyung Joon, Lee Seong Jin
机构信息
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
出版信息
Biochem Biophys Res Commun. 2014 Nov 7;454(1):36-41. doi: 10.1016/j.bbrc.2014.10.060. Epub 2014 Oct 18.
In this study, we evaluated the effect of the hsp70 inhibitor VER155008 on survival of anaplastic thyroid carcinoma (ATC) cells. In ATC cells, VER155008 increased the percentages of dead cells and vacuolated cells. VER155008 did not lead to the cleavage of caspase-3 protein regardless of pretreatment with z-VAD-fmk. VER155008 increased LC3-II protein levels but the protein levels were not changed by autophagy inhibitors. VER155008 caused the dilatation of endoplasmic reticulum (ER), and the increased mRNA levels of Bip and CHOP, suggesting paraptosis. VER155008-induced paraptosis was attenuated by pretreatment with cycloheximide. In conclusion, VER155008 induces paraptosis characterized by cytoplasmic vacuolation, independence of caspase, dilatation of ER and induction of ER stress markers in ATC cells. Moreover, VER155008-induced paraptosis requires de novo protein synthesis in ATC cells.
在本研究中，我们评估了热休克蛋白70（hsp70）抑制剂VER155008对间变性甲状腺癌（ATC）细胞存活的影响。在ATC细胞中，VER155008增加了死亡细胞和空泡化细胞的百分比。无论是否用z-VAD-fmk预处理，VER155008均未导致半胱天冬酶-3蛋白的裂解。VER155008增加了微管相关蛋白1轻链3-II（LC3-II）蛋白水平，但自噬抑制剂未改变该蛋白水平。VER155008导致内质网（ER）扩张，并增加了结合免疫球蛋白蛋白（Bip）和C/EBP同源蛋白（CHOP）的mRNA水平，提示非凋亡性程序性细胞死亡（paraptosis）。用环己酰亚胺预处理可减弱VER155008诱导的paraptosis。总之，VER155008诱导ATC细胞发生paraptosis，其特征为细胞质空泡化、不依赖半胱天冬酶、内质网扩张以及内质网应激标志物的诱导。此外，VER155008诱导的paraptosis需要ATC细胞重新合成蛋白质。
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