1. Academic Validation
  2. Z-360, a novel cholecystokinin-2/gastrin receptor antagonist, inhibits gemcitabine-induced expression of the vascular endothelial growth factor gene in human pancreatic cancer cells

Z-360, a novel cholecystokinin-2/gastrin receptor antagonist, inhibits gemcitabine-induced expression of the vascular endothelial growth factor gene in human pancreatic cancer cells

  • Biol Pharm Bull. 2010;33(2):216-22. doi: 10.1248/bpb.33.216.
Nobuyoshi Kobayashi 1 Koichi Seto Yuki Orikawa Hiroki Hamano Koji Yoshinaga Mineo Takei
Affiliations

Affiliation

  • 1 Central Research Laboratories, Zeria Pharmaceutical Co., Ltd, 2512-1 Oshikiri, Kumagaya, Saitama 360-0111, Japan.
Abstract

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.

Figures