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Lovastatin, but not orlistat, reduces intestinal polyp volume in an ApcMin/+ mouse model
- Source :
- Oncology Reports. 36:893-899
- Publication Year :
- 2016
- Publisher :
- Spandidos Publications, 2016.
-
Abstract
- 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 (ω)-3 polyunsaturated fatty acid (PUFA)- or olive oil-enriched diet reduced the polyp number and volume in ApcMin/+ mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)β/α ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in ApcMin/+ mice, in order to confirm previous data obtained with ω‑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 ERα. Moreover, the overexpression of ERα was associated with a statistically significant increase in PES1, Shh and Gli1 protein levels, considered ERα-related molecular targets.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
Intestinal polyp
Gene Expression
Cell Cycle Proteins
Biology
Zinc Finger Protein GLI1
Lactones
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Fatty Acids, Omega-3
medicine
Animals
Estrogen Receptor beta
Hedgehog Proteins
Lovastatin
Olive Oil
Fatty acid synthesis
Cell Proliferation
Orlistat
chemistry.chemical_classification
Cholesterol
Estrogen Receptor alpha
Intestinal Polyps
Proteins
RNA-Binding Proteins
General Medicine
Disease Models, Animal
Fatty acid synthase
030104 developmental biology
Endocrinology
Oncology
chemistry
Apoptosis
030220 oncology & carcinogenesis
biology.protein
Fatty Acid Synthases
medicine.drug
Polyunsaturated fatty acid
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....2d657cc697ff8b1289d2929140e74af8