title: Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system.
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-β1)-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-β1 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.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.|Cancer Metastasis Institute, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Q-B
authors.initials: QB
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: B-H
authors.initials: BH
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.|Department of General Surgery, The People's Hospital of Taizhou City, Taizhou, China.
authors.forename: K-Z
authors.initials: KZ
authors.lastname: Zhang
authors.affiliation: School of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors.forename: X-T
authors.initials: XT
authors.lastname: Meng
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.|Cancer Metastasis Institute, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Q-A
authors.initials: QA
authors.lastname: Jia
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.|Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Q-B
authors.initials: QB
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: X-D
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: D-N
authors.initials: DN
authors.lastname: Ma
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: B-G
authors.initials: BG
authors.lastname: Ye
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: Z-G
authors.initials: ZG
authors.lastname: Ren
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: H-C
authors.initials: HC
authors.lastname: Sun
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
authors.forename: Z-Y
authors.initials: ZY
authors.lastname: Tang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013550:Swimming; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D017448:Receptors, Dopamine D2; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases