RRC ID 68682
Author Hayakawa Y, Hirata Y, Sakitani K, Nakagawa H, Nakata W, Kinoshita H, Takahashi R, Takeda K, Ichijo H, Maeda S, Koike K.
Title Apoptosis signal-regulating kinase-1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer.
Journal Cancer Sci
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.
Volume 103(12)
Pages 2181-5
Published 2012-12-1
DOI 10.1111/cas.12024
PMID 23110662
PMC PMC7659227
MeSH Animals Antineoplastic Agents / pharmacology* Apoptosis* Cell Line, Tumor Cell Proliferation HeLa Cells Humans MAP Kinase Kinase Kinase 5 / antagonists & inhibitors* MAP Kinase Kinase Kinase 5 / genetics MAP Kinase Kinase Kinase 5 / metabolism* Mice Mice, Nude Neoplasm Transplantation Receptor, ErbB-2 / genetics Receptor, ErbB-2 / metabolism Stomach Neoplasms / drug therapy* Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology Transplantation, Heterologous Up-Regulation
IF 4.966
Resource
Human and Animal Cells MKN45(RCB1001) MKN74(RCB1002) MKN7(RCB0999) HuG1-N(RCB1179)