Abstract
This study was made to explore the effects of acetazolamide on tumor growth,metastasis and the possible mechanisms. The mice bearing with Lewis lung carcinomaswere taken as the animal model. The effects of acetazolamide were compared with thecombination treatment of NaHCO3 on tumor growth, metastasis and carbonic anhydraseactivity in lung and tumor tissues using imidazole-Tris technique. And also the possible roleof AQP1 in tumor tissues was investigated by Western blot and immuno-histochemicalanalysis. Results showed that acetazolamide alone could sharply reduce the number of lungmetastasis and primary tumor growth, and appeared in a dose-dependent manner.Acetazolamide significantly inhibited carbonic anhydrase activity in tumor tissue. After theaddition of NaHCO3, the suppression of acetazolamide on tumor growth, number ofmetastasis and carbonic anhydrase activity in primary tumor tissue could not be alteredsignificantly, but the inhibitory rate of metastasis in lung and carbonic anhydrase activity inlung tissue appeared to show a reversal trend in the dose dependency from the acetazolamidetreatment alone. The exactly mechanisms need to be clarified in future. Western blot andimmunohistochemical analysis demonstrated that AQP1 expression in the tumor tissue washigher than both tissue of normal and treated with acetazolamide treatment alone.Combination with NaHCO3 could not synergistically inhibit the expression of AQP1 withacetazolamide. The results suggested that the mechanism of acetazolamide on anti-tumor especially on its anti-metastasis actions might partly involve either inhibiting the carbonic anhydrase activity or reducing AQP1 water channel protein expression, whatever if treated with or without NaHCO3.
Highlights
Tumor metastasis is the major characteristic of carcinoma and the direct cause of clinical death
To determine whether combination treatment with acetazolamide and NaHCO3 could reduce the number of lung metastasis synergistically, we compared the effect of two medications
We found that acetazolamide treatment alone could sharply reduce the number of lung metastasis and primary tumor growth
Summary
Tumor metastasis is the major characteristic of carcinoma and the direct cause of clinical death. Carbonic anhydrases (CA) are a family of zinc-binding metalloproteinases that catalyze reversible hydration of carbon dioxide, produce H+ and HCO3-, and induce pH decrease [1]. Some CA isozymes (CA IV, IX, XII) were prominently found to be expressed only in tumor cells [2]. The cell surface CA might play an important role in controlling the level of protons and bicarbonate in the immediate vicinity of tumor cells by sensing pH and tipping the proton balance across the cell membrane. It has been shown that acidic pH enhances invasive behavior of tumor cells [3, 4]. Acetazolamide is a kind of sulfanilamide served as a carbonic anhydrase inhibitor
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