Acetazolamide inhibits aquaporin-1 expression and colon cancer xenograft tumor growth

Hepatogastroenterology. 2011 Sep-Oct;58(110-111):1502-6. doi: 10.5754/hge11154. Epub 2011 Jul 15.

Abstract

Background/aims: To study the effects of water channel protein inhibitor acetazolamide on xenograft tumor growth of colon cancer in nude mice.

Methodology: Setting up human colon cancer model in nude mice, mice were randomly divided into two groups as experimental group and control group. Acetazolamide was given at a volume of 0.1mL per mice (40mg/kg/d, ig) in experimental group, while the same volume of sterile saline was given in control group (ig). After 21 days, protein and m-RNA levels of AQP-1 in tumor tissues from two groups were detected respectively by Western blot and RT-PCR to evaluate the treatment effects. AQP-1, VEGF and CD34 expression was detected by immunohistochemistry, simultaneously.

Results: Acetazolamide (40mg/kg/d, ig) significantly inhibited the xenograft tumor growth of colon cancer in nude mice. The inhibition rate was 88.28%. In comparison with the control group, AQP-1 protein and mRNA level were significantly reduced in the experimental group (p<0.01). AQP-1, VEGF and CD34 expression in experimental group were positively correlated between each other (p<0.01).

Conclusions: Acetazolamide can suppress the xenograft tumor growth by inhibiting the expression of AQP-1.

MeSH terms

  • Acetazolamide / pharmacology*
  • Animals
  • Antigens, CD34 / metabolism
  • Aquaporin 1 / metabolism*
  • Blotting, Western
  • Colonic Neoplasms / drug therapy*
  • Female
  • Immunoenzyme Techniques
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy*
  • Real-Time Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD34
  • Vascular Endothelial Growth Factor A
  • Aquaporin 1
  • Acetazolamide