The angiotensin II type 1 receptor blocker candesartan suppresses proliferation and fibrosis in gastric cancer

Cancer Lett. 2014 Dec 1;355(1):46-53. doi: 10.1016/j.canlet.2014.09.019. Epub 2014 Sep 16.

Abstract

Gastric cancer with peritoneal dissemination has poor clinical prognosis because of the presence of rich stromal fibrosis and acquired drug resistance. Recently, Angiotensin II type I receptor blockers such as candesartan have attracted attention for their potential anti-fibrotic activity. We examined whether candesartan could attenuate tumor proliferation and fibrosis through the interaction between gastric cancer cell line (MKN45) cells and human peritoneal mesothelial cells. Candesartan significantly reduced TGF-β1 expression and epithelial-to-mesenchymal transition-like change, while tumor proliferation and stromal fibrosis were impaired. Targeting the Angiotensin II signaling pathway may therefore be an efficient strategy for treatment of tumor proliferation and fibrosis.

Keywords: Angiotensin II; Fibrosis; Gastric cancer; Peritoneal dissemination; TGF-β.

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Benzimidazoles / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Fibrosis
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Omentum / drug effects
  • Omentum / metabolism
  • Omentum / pathology
  • Receptor, Angiotensin, Type 1 / drug effects*
  • Receptor, Angiotensin, Type 1 / metabolism
  • Signal Transduction / drug effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Tetrazoles / pharmacology*
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • AGTR1 protein, human
  • Angiotensin II Type 1 Receptor Blockers
  • Antineoplastic Agents
  • Benzimidazoles
  • Receptor, Angiotensin, Type 1
  • TGFB1 protein, human
  • Tetrazoles
  • Transforming Growth Factor beta1
  • candesartan