title: Apoptosis signal-regulating kinase-1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer.
abstract: Aside from the human epidermal growth factor receptor-2 (HER2)-targeting agent trastuzumab, molecular targeting therapy for gastric cancer (GC) has not been established. We previously reported that apoptosis signal-regulating kinase-1 (ASK1) was upregulated in human GC and that overexpression of ASK1 promoted GC cell proliferation. Here, we investigated the effect of ASK1 inhibitor K811 on GC cells. K811 efficiently prevented cell proliferation in cell lines with high ASK1 expression and in HER2-overexpressing GC cells. Treatment with K811 reduced sizes of xenograft tumors by downregulating proliferation markers. These results indicate that ASK1 inhibition prevents GC cell growth in vitro and in vivo, suggesting that ASK1 inhibitors can be potent therapeutic drugs for GC.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. yhayakawa-tky@umin.ac.jp
authors.forename: Yoku
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sakitani
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Wachiko
authors.initials: W
authors.lastname: Nakata
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Ryota
authors.initials: R
authors.lastname: Takahashi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Takeda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
authors.forename: Shin
authors.initials: S
authors.lastname: Maeda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006367:HeLa Cells; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D048848:MAP Kinase Kinase Kinase 5; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C482858:MAP3K5 protein, human