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

Nobuyoshi Kobayashi, Koichi Seto, Yuki Orikawa, Hiroki Hamano, Koji Yoshinaga, Mineo Takei

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)216-222
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume33
Issue number2
DOIs
Publication statusPublished - 01-02-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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