Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer

Michio Kosugi, Akira Miyajima, Eiji Kikuchi, Takeo Kosaka, Yutaka Horiguchi, Masaru Murai

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Several authors have investigated the antitumor activity of angiotensin II type 1 receptor (AT1R) antagonists, which are widely used as antihypertensive drugs. In this study, we evaluated the efficacy of the AT1R antagonist candesartan against bladder cancer. For the study in vitro, human bladder cancer cells (KU-19-19) were cultured with and without angiotensin II (A II) and candesartan, and cell viability and vascular endothelial growth factor (VEGF) secretion were analyzed. Also for the study in vivo, a tumor xenograft model was prepared in nude mice using KU-19-19 cells. Mice were administered candesartan daily by oral gavage, and paclitaxel via intravenous infusion. Microvessel density, VEGF expression, and apoptosis were investigated. Candesartan did not induce direct toxicity in KU-19-19 cells, but VEGF was significantly lower in candesartan-treated cells than in the A II-treated control cells. In mice, candesartan, paclitaxel and candesartan-paclitaxel significantly suppressed tumor growth to 46.0%, 35.8% and 17.3%, respectively, of the tumor volume in the control group, showing that combined treatment significantly inhibited tumor growth compared to the candesartan group. Microvessel density and VEGF were significantly decreased in the candesartan and candesartan-paclitaxel groups compared to the control group. The apoptotic index was significantly increased in the paclitaxel and candesartan-paclitaxel groups compared to the control and candesartan groups. In our experimental model, candesartan prevented bladder cancer growth by inhibiting angiogenesis. Furthermore, combined treatment with candesartan and paclitaxel enhanced paclitaxel-induced cytotoxicity. These results suggest that the AT1R antagonist candesartan may be a candidate for innovative therapy for bladder cancer.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalHuman Cell
Volume20
Issue number1
DOIs
Publication statusPublished - 2007 Feb

Fingerprint

Angiotensin II Type 1 Receptor Blockers
Heterografts
Urinary Bladder Neoplasms
Paclitaxel
Growth
Neoplasms
Vascular Endothelial Growth Factor A
candesartan
Microvessels
Angiotensin II
Control Groups
Investigational Therapies
Tumor Burden

Keywords

  • Bladder cancer
  • Candesartan
  • KU-19-19
  • Paclitaxel
  • VEGF

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

Cite this

Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer. / Kosugi, Michio; Miyajima, Akira; Kikuchi, Eiji; Kosaka, Takeo; Horiguchi, Yutaka; Murai, Masaru.

In: Human Cell, Vol. 20, No. 1, 02.2007, p. 1-9.

Research output: Contribution to journalArticle

Kosugi, Michio ; Miyajima, Akira ; Kikuchi, Eiji ; Kosaka, Takeo ; Horiguchi, Yutaka ; Murai, Masaru. / Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer. In: Human Cell. 2007 ; Vol. 20, No. 1. pp. 1-9.
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