title: Antitumor activity of YM155, a selective survivin suppressant, in combination with cisplatin in hepatoblastoma.
abstract: Cisplatin (CDDP) is a chemotherapeutic drug that is often used for the treatment of hepatoblastoma. However, many patients acquire resistance to therapeutic agents leading to local and distant treatment failure. It has been shown that suppression survivin contributed to the inhibition of tumor growth and enhanced chemotherapeutic sensitivity in several types of cancer. The aim of the present study was to determine whether treatment with sepantronium bromide (YM155), a novel small molecule inhibitor of survivin, enhanced the sensitivity of CDDP to hepatoblastoma cells, leading to the therapeutic efficacy of cisplatin. In vitro and in vivo models were used to examine the anticancer efficacy of YM155, either as a monotherapy or in combination with CDDP to identify more effective therapeutics against hepatoblastoma. The results showed that survivin expression was upregulated in hepatoblastoma tissues and cell lines, and that YM155 inhibited survivin expression in hepatoblastoma cells in a dose-dependent manner. YM155 enhanced sensitivity of CDDP to human HepG2 and HuH-6 hepatoblastoma cells. The YM155 combination with CDDP in hepatoblastoma cells significantly decreased cell proliferation and formation, and induced cell apoptosis than either agent alone. In a mouse xenograft model, YM155 combined with CDDP significantly suppressed tumor growth compared to the monotherapy. Taken together, these findings suggested that the combination of YM155 and CDDP is a promising drug candidate for the treatment of hepatoblastoma.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: The Nursing Department of the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The Nursing Department of the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Nursing Department of the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Kang
authors.affiliation: The Nursing Department of the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000494:pharmacology; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009285:Naphthoquinones / Q000008:administration & dosage* / Q000494:pharmacology; D000077022:Survivin; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D007093:Imidazoles; D051034:Inhibitor of Apoptosis Proteins; D009285:Naphthoquinones; D000077022:Survivin; D002945:Cisplatin; C523798:sepantronium