title: YM155 exerts a growth inhibitory effect on human osteosarcoma in vitro and in vivo.
abstract: YM155, a novel small-molecule inhibitor of survivin, is known to exert antitumor effects on various cancers, including breast, prostate and lung cancer. However, there are few studies describing the inhibitory effect of YM155 on human osteosarcoma (OS) which highly expresses survivin. Here, we tested the effects of YM155 on OS cells by several in vitro experiments. It was found that YM155 inhibited cell proliferation, colony formation, migration and invasion, induced cell apoptosis, as well as increased caspase-3, -8 and -9 activity in the OS cell lines in a dose-dependent manner. We also found that YM155 suppressed Mcl-1 and survivin expression without affecting the expression of anti-apoptotic proteins X-linked inhibitor of apoptosis (XIAP) and Bcl-2. In addition, YM155 decreased phosphoinositide 3-kinase (PI3K) and AKT expression without effecting total PI3K and AKT in the OS cell lines, which contributed to suppression of OS tumor growth at least in part. In addition, YM155 also suppressed tumor growth in vivo, reducing the size of OS MG63 cell xenografts. Taken together, the findings revealed that YM155 suppresses the tumor growth of OS in vitro and in vivo, suggesting that YM155 has potential as a therapeutic agent for the treatment of OS.
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Lianjun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D009285:Naphthoquinones; C523798:sepantronium