Survivin suppressor (YM155) enhances chemotherapeutic efficacy against canine histiocytic sarcoma in murine transplantation models.
Histiocytic sarcoma (HS) in dogs exhibits aggressive clinical and biological behavior. Currently, no effective treatments are available for dogs with HS. Survivin, a member of a family of apoptosis protein inhibitors, could serve as a potential therapeutic target in several canine cancers. Sepantronium bromide (YM155) has recently been established as a novel survivin-targeting agent. The aim of this study was to use YM155 as a tool for evaluating survivin-targeted therapies against dogs with HS, and to investigate how YM155 treatment affects antitumor and chemotherapeutic efficacies in murine xenograft models using canine HS cells. The results showed that in HS cells with lomustine (CCNU) resistance, YM155 treatment suppressed both the cell-growth potential and cell resistance to CCNU, which essentially increases the chemotherapy efficacy in the murine models. The evidence presented here supports the favorable preclinical evaluation that survivin-targeted therapies might be effective against HS in dogs.
Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Japan; Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, Japan.
Hiroki
H
Yamazaki
Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Japan. Electronic address: staka@vetmed.hokudai.ac.jp.
Satoshi
S
Takagi
Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Japan.
Kenji
K
Hosoya
Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Japan.
Masahiro
M
Okumura
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000188:drug therapy* / Q000209:etiology; D004285:Dogs; D054747:Histiocytic Sarcoma / Q000188:drug therapy / Q000209:etiology / Q000662:veterinary*; D007093:Imidazoles / Q000627:therapeutic use*; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D023421:Models, Animal; D009285:Naphthoquinones / Q000627:therapeutic use*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D000077022:Survivin
D000970:Antineoplastic Agents; C117749:Birc5 protein, mouse; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D012097:Repressor Proteins; D000077022:Survivin; C523798:sepantronium
Chemoresistance; Dog; Histiocytic sarcoma; Survivin