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Abstract

EVALUATION OF THE ANTICARCINOGENIC EFFECT OF SOME PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR LIGANDS ON DIMETHYLBENZ (α) ANTHRACENE INDUCED MAMMARY TUMOR IN FEMALE RATS

Remonda E. Rizk, Wessam F. El-Hadidy*, Malak A. Zoheir, Nesrine S. Ibrahim

ABSTRACT

 

Introduction: Breast cancer is the leading cause of cancer death among
females worldwide. Peroxisome proliferator activated receptors
(PPARs) are one of several nuclear receptors involved in the biology
of breast cancer. Aim: Compare the effect of fenofibrate (PPARα
ligand), pioglitazone (PPAR γ ligand) and omega-3 (PPARα, γ ligand)
and their probable mechanisms of action on 7, 12 dimethylbenz (α)
anthracene (DMBA)-induced mammary carcinoma in female rats.
Methods: Fifty female Waister albino rats were utilized, with ten
serving as plain controls. The remaining were subjected to induction of
mammary carcinomas by oral intubation with a single dose of 20 mg
DMBA suspended in one ml of sesame oil. After the appearance of
mammary tumors, rats were randomly assigned to 4 orally-treated
groups: untreated, fenofibrate, pioglitazone and omega-3-treated for 28
days. Assessed parameters: Percentage change of tumor volume, serum and tumor tissue
vascular endothelial growth factor levels, tumor caspase-3 and cyclooxygenase-2
concentrations, as well as immunohistochemical detection of Ki-67 expression. Results: The
untreated rats had progressive increase in mammary tumor volume. Treatment with
fenofibrate, pioglitazone or omega-3 significantly reduced the rate of tumor growth via
antiangiogenic, proapoptotic, antiproliferative and anti-inflammatory effects. Conclusion: Fenofibrate, pioglitazone and omega-3 exerted anti-tumor effects on breast cancer induced in rats via numerous mechanisms of action.

Keywords: Peroxisome proliferator activated receptors, fenofibrate, pioglitazone, omega-3, cyclooxygenase-2, induced mammary tumor.


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