著者
Nobuyoshi Kobayashi Koichi Seto Yuki Orikawa Hiroki Hamano Koji Yoshinaga Mineo Takei
出版者
The Pharmaceutical Society of Japan
雑誌
Biological and Pharmaceutical Bulletin (ISSN:09186158)
巻号頁・発行日
vol.33, no.2, pp.216-222, 2010-02-01 (Released:2010-02-01)
参考文献数
33
被引用文献数
6 10

Z-360 is a novel cholecystokinin (CCK)-2/gastrin receptor antagonist that is being developed for the treatment of pancreatic adenocarcinoma in combination with gemcitabine. A previous study shows that the co-administration of Z-360 with gemcitabine significantly prolonged the survival of mice with orthotopically implanted human pancreatic adenocarcinoma cell lines. To clarify the therapeutic effects of Z-360 in combined with gemcitabine, we analyzed gene expression. When gemcitabine was administered, CCK-2/gastrin receptor expression was induced in an orthotropic xenograft model; the result indicating that Z-360 could act on gemcitabine-sensitive cells. Both in vitro and in vivo studies showed that gemcitabine increased the expression of vascular endothelial growth factor A (VEGFA), a prognostic factor for survival in pancreatic cancer, while Z-360 suppressed this induction of VEGFA gene expression. These results help to explain how Z-360 prolongs survival when used in combination with gemcitabine.