Efficacy of an anti-cancer strategy targeting SET in canine osteosarcoma

被引:6
作者
Tsuji, Shunya [1 ]
Ohama, Takashi [1 ]
Nakagawa, Takayuki [2 ,3 ]
Sato, Koichi [1 ]
机构
[1] Yamaguchi Univ, Lab Vet Pharmacol, Joint Fac Vet Med, 1677-1 Yoshida, Yamaguchi 7538515, Japan
[2] Univ Tokyo, Grad Sch Agr & Life Sci, Lab Vet Surg, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan
[3] Univ Tokyo, Grad Sch Agr & Life Sci, Vet Med Ctr, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1138657, Japan
关键词
canine; osteosarcoma; protein phosphatase 2A (PP2A); SET; PROTEIN PHOSPHATASE 2A; CELL-LINE; THERAPY; ESTABLISHMENT; MECHANISMS; ADJUVANT; GROWTH; CANCER;
D O I
10.1292/jvms.19-0311
中图分类号
S85 [动物医学(兽医学)];
学科分类号
0906 ;
摘要
Osteosarcoma (OSA) is the most common bone tumor in dogs. Protein phosphatase 2A (PP2A), an evolutionary conserved serine/threonine protein phosphatase, is a crucial tumor suppressor. SET is a PP2A inhibitory protein that directly interacts with PP2A and suppresses its phosphatase activity. SET has been reported as a contributor of wide range of human and dog tumor malignancies. However, the role of SET in canine OSA (cOSA) remains unknown. In this study, we investigated the role of SET in cOSA by using 2 cOSA cell lines: POS (primary origin) and HM-POS ( metastatic origin). Knockdown (KD) of SET expression was noted to slightly suppress POS cell proliferation only. Furthermore, SET KD effectively suppressed colony formation ability of both POS and HM-POS cells. SET KD was observed to repress ERK1/2, mTOR, E2F1, and NF-kappa B signaling in HM-POS cells, whereas it inhibited only ERK1/2 signaling in POS. Further, it was observed that SET-targeting drug, FTY720, exerted anti-cancer effects in both POS and HM-POS cells. Moreover, the drug also enhanced the anti-cancer effect of cisplatin. The data suggested that a combination therapy, based on SET targeting drugs and cisplatin, could be a potent strategy for cOSA.
引用
收藏
页码:1424 / 1430
页数:7
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