3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, fluvastatin, as a novel agent for prophylaxis of renal cancer metastasis

Akio Horiguchi, Makoto Sumitomo, Junichi Asakuma, Takako Asano, Tomohiko Asano, Masamichi Hayakawa

研究成果: Article査読

84 被引用数 (Scopus)

抄録

Purpose: Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also called statins, are currently used widely as a safe, effective therapeutic in the treatment of hypercholesterolemia. Recently, statins have been recognized for their activity against cancer. In the present study, we examined the effect of a synthetic statin, fluvastatin, on the development of renal cancer. Experimental Design: The effects of fluvastatin on cell viability, cell cycle, in vitro angiogenesis, and invasive properties were examined in murine renal cancer cell Renca. The changes in cell cycle-associated proteins, p21Waf1/Cip1 and p53, and rac1 phosphorylation were analyzed by Western blotting. The prophylactic efficacy of fluvastatin to murine pulmonary metastasis of Renca was examined. Results: Fluvastatin inhibited in vitro growth of Renca cells in a time- and dose-dependent manner, with up to 70% inhibition at a concentration of 10 μmol/L. This inhibitory effect was due to cell cycle arrest at the G1 phase and induction of apoptosis accompanied by ap-regulation of p21Waf1/Cip1 and p53. The invasive properties of Renca cells through Matrigel were inhibited by fluvastatin, with decreased phosphorylation of rac1. In vitro angiogenesis was also inhibited by fluvastatin. Furthermore, oral administration at doses of 1 to 10 mg/kg/d, for 12 days after inoculation of Renca eels via the tail vein, significantly decreased the amount of pulmonary metastasis. Conclusions: Because our results suggest that fluvastatin may effectively inhibit in vitro tumor growth, invasion, angiogenesis, and metastasis of Renca cells, oral administration of fluvastatin could be a novel, safe, and effective agent for preventing metastasis of renal cancer.

本文言語English
ページ(範囲)8648-8655
ページ数8
ジャーナルClinical Cancer Research
10
24
DOI
出版ステータスPublished - 15-12-2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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