Apoptosis signal-regulating kinase-1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer

被引：44

作者：

Hayakawa, Yoku ^{[1
]}

Hirata, Yoshihiro ^{[1
]}

Sakitani, Kosuke ^{[1
]}

Nakagawa, Hayato ^{[1
]}

Nakata, Wachiko ^{[1
]}

Kinoshita, Hiroto ^{[1
]}

Takahashi, Ryota ^{[1
]}

Takeda, Kohsuke ^{[2
,4
]}

Ichijo, Hidenori ^{[2
]}

Maeda, Shin ^{[1
,3
]}

Koike, Kazuhiko ^{[1
]}

机构：

[1] Univ Tokyo, Dept Gastroenterol, Grad Sch Med, Tokyo, Japan

[2] Univ Tokyo, Lab Cell Signaling, Grad Sch Pharmaceut Sci, Tokyo, Japan

[3] Yokohama City Univ, Dept Gastroenterol, Yokohama, Kanagawa 232, Japan

[4] Nagasaki Univ, Div Cell Regulat, Grad Sch Biomed Sci, Nagasaki 852, Japan

来源：

CANCER SCIENCE | 2012年 / 103卷 / 12期

关键词：

ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; TUMOR-GROWTH; CELLS; PATHWAY; CHEMOTHERAPY; ASK1;

D O I：

10.1111/cas.12024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (Cancer Sci 2012; 103: 2181-2185)

引用

页码：2181 / 2185

页数：5

共 23 条

[21] Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1 [J].