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1.
Oncogene ; 35(31): 4122-31, 2016 08 04.
Article in English | MEDLINE | ID: mdl-26686088

ABSTRACT

Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-ß1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-ß1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.


Subject(s)
Liver Neoplasms, Experimental/pathology , Receptors, Dopamine D2/physiology , Swimming , Animals , Disease Models, Animal , Epithelial-Mesenchymal Transition , Extracellular Signal-Regulated MAP Kinases/physiology , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Time Factors , Transforming Growth Factor beta1/physiology , Xenograft Model Antitumor Assays
2.
Gen Comp Endocrinol ; 194: 198-207, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24076539

ABSTRACT

Molt, a natural behavior that is initiated at the end of a lay cycle in birds, is implicated in the regression of the reproductive system in birds followed by a rejuvenation of egg-laying potential. The aim of the present study was to evaluate the physiological basis for the apparent rejuvenation of egg production that occurs following molting. Eighty-three-week-old Hy-line hens, were obtained and subjected to forced molting. Blood and tissue samples were obtained at the beginning of molt (at 83 weeks of age), during molt (at 85 weeks of age) and postmolt (at 89 weeks of age). The laying performance, egg quality, blood parameters and gene expression in the liver and the ovary were investigated before, during and after molt. There was an obvious increase in the postmolt laying rate from 70% premolt to 93% postmolt. Eggshell thickness, albumin height, Haugh unit and egg shape index were all significantly improved after molt. The circulating levels of estrogen and progesterone were lower in the postmolt hens, whereas the concentrations of luteinizing hormone and follicle stimulating hormone were not significantly affected by molt. These results indicate that enhanced hepatic yolk precursor synthesis and secretion contribute to increased postmolt laying performance. Molt enhanced the sensitivity of sex hormones in F1 follicles. Augmented gene expression in the ovary was involved in the rejuvenation of the reproductive performance of molted hens. These results suggest that facilitated yolk-precursor uptake by follicles is involved in the rejuvenation of the reproductive performance of molted hens.


Subject(s)
Ovary/physiology , Rejuvenation/physiology , Reproduction/physiology , Animals , Chickens , Female , Molting/physiology , Ovarian Follicle/metabolism , Ovarian Follicle/physiology , Ovary/metabolism
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