Effects of Exercise Training Together With Tamoxifen in Reducing Mammary Tumor Burden in Mice: Possible Underlying Pathway of Mir-21 Publisher Pubmed



Khori V¹ ; Amani Shalamzari S² ; Isanejad A^{3, 4} ; Alizadeh AM² ; Alizadeh S⁵ ; Khodayari S² ; Khodayari H⁶ ; Shahbazi S⁷ ; Zahedi A² ; Sohanaki H⁸ ; Khaniki M⁹ ; Mahdian R¹⁰ ; Saffari M¹¹ ; Fayad R¹²
Source: European Journal of Pharmacology Published:2015

Abstract

Exercise training has an anti-tumor effect and can reduce tumor growth; however, the exact underlying mechanisms of its protective effects are still obscure. MicroRNA (miR)-21 is a predictor in cancer survival, and has a potential use as an indicator of therapeutic outcome in breast malignancies. Forty-eight female BALB/c mice were equally divided into six groups to investigate the effects of interval exercise training with tamoxifen on miR-21 expression and its possible assumed mechanisms in an estrogen receptor-positive breast cancer model. ELISA, immunohistochemistry, western blot, qRT-PCR assays were performed at the end of the study. Tumor size was significantly declined in exercise training and tamoxifen groups compared to tumor group (P<0.05). Expression of miR-21 was significantly down-regulated in trained and tamoxifen treated mice in comparison with tumor group (P<0.05). Exercise training was as effective as tamoxifen treatment in decreasing serum estradiol and ER-α expression (P<0.05). Exercise training and tamoxifen reduced tumor IL-6 levels, NF-kB and STAT3 expressions, and up-regulated TPM1 and PDCD4 expressions (P<0.05). Both exercise and tamoxifen had synergistic effects in reducing miR-21 and Bcl-2, and up-regulating PDCD4 expression. Results showed that interval exercise training may reduce mammary tumor burden in mice through possible underlying pathway of miR-21. © 2015 Elsevier B.V. All rights reserved.