الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer is one of the most common and lethal cancers among women worldwide. Recently, the antiumorigenic effects of cannabinoids, the active component of marijuana, have emerged as an exciting field in cancer research. The aim of the present study was to evaluate the effect of mixed CB1/CB2 synthetic cannabinoid agonist WIN-55,212-2 on tumor development and cannabinoid receptors (CB1 and CB2) expression in N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in female rats. Administration of WIN-55,212-2 significantly decreased tumor incidence, tumor frequency per animal, average tumor volume, and lengthened the latency period compared to NMU group. A histopathological analysis of mammary tumors revealed a shift from poorly-differentiated IDCs in NMU group to well-differentiated and benign tumors in WIN-55,212-2-treated groups. Enhanced CB1 and CB2 expression was significantly observed in malignant compared to benign and normal breast tissues. However, the administration of WIN-55,212-2 showed higher CB2R expression than CB1R, especially in well-differentiated and benign breast lesions. WIN-55,212-2 also reduced serum concentrations of prolactin, estradiol, progesterone, ALT, AST, urea and creatinine compared to NMU group. This study suggests the marked chemopreventive and antineoplastic activity of WIN-55,212-2 against NMU-induced mammary carcinogenesis and the possible role of cannabinoid receptors in the pathophysiology of breast carcinoma.