title: Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21.
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.
authors: Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors: Vahid
authors: V
authors: Khori
authors: Cancer Research Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran.
authors: Sadegh
authors: S
authors: Amani Shalamzari
authors: Immunological Response Research Center, Shahed University, Tehran, Iran; Physical Education Department, Shahed University, Tehran, Iran.
authors: Amin
authors: A
authors: Isanejad
authors: Cancer Research Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran. Electronic address: aalizadeh@sina.tums.ac.ir.
authors: Ali Mohammad
authors: AM
authors: Alizadeh
authors: Hematology Department, Allied Medical School, Tehran University of Medical Sciences, Tehran, Iran.
authors: Shaban
authors: S
authors: Alizadeh
authors: Cancer Research Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran.
authors: Saeed
authors: S
authors: Khodayari
authors: Cancer Models Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors: Hamid
authors: H
authors: Khodayari
authors: Medical Genetics Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Shirin
authors: S
authors: Shahbazi
authors: Cancer Research Center, Tehran University of Medical Sciences, Tehran 1419733141, Iran.
authors: Ali
authors: A
authors: Zahedi
authors: Physiology Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Hamid
authors: H
authors: Sohanaki
authors: Pathology Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mahmood
authors: M
authors: Khaniki
authors: Department of Molecular Medicine, Pasteur Institute of Iran, Tehran, Iran.
authors: Reza
authors: R
authors: Mahdian
authors: Medical Genetics Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors: Mojtaba
authors: M
authors: Saffari
authors: Colon Cancer Center, South Carolina University, United States of America.
authors: Raja
authors: R
authors: Fayad
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D015536:Down-Regulation; D004958:Estradiol / Q000097:blood; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects* / Q000235:genetics
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004958:Estradiol; D015850:Interleukin-6; D035683:MicroRNAs; D013629:Tamoxifen; C577686:interleukin-6, mouse; C531950:MIRN21 microRNA, mouse
keywords: Breast cancer; Interval exercise training; Tamoxifen; miR-21