Lovastatin, But Not Orlistat, Reduces Intestinal Polyp Volume In An Apc(Min/+) Mouse Model

The statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and orlistat, an inhibitor of fatty acid synthase (FAS), inhibit tumor cell growth by restricting cholesterol and fatty acid synthesis, respectively. We previously demonstrated that an omega (omega)-3 polyunsaturated fatty acid (PUFA)- or olive oil-enriched diet reduced the polyp number and volume in Apc(Min/+) mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)beta/alpha ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in Apc(Min/+) mice, in order to confirm previous data obtained with omega-3-PUFAs and olive oil. As expected, the use of lovastatin and orlistat significantly reduced HMGCoAR and FAS enzymatic activities and gene expression in colonic tissues, but did not affect the number of intestinal polyps, while there was a statistically significant reduction in polyp volume only in the mouse group treated with lovastatin. In the mice receiving orlistat, we observed a significant increase in cell proliferation in the polyp tissue, as well as enhanced expression of ER alpha. Moreover, the overexpression of ER alpha was associated with a statistically significant increase in PES1, Shh and Glil protein levels, considered ERa-related molecular targets.