Anti-tumoral effects of exercise on hepatocellular carcinoma growth.

Saran, Uttara; Guarino, Maria; Rodriguez Navarro, Sarai; Simillion, Cedric; Montani, Matteo; Foti, Michelangelo; Humar, Bostjan; St-Pierre, Marie; Dufour, Jean-François (2018). Anti-tumoral effects of exercise on hepatocellular carcinoma growth. Hepatology communications, 2(5), pp. 607-620. Wiley 10.1002/hep4.1159

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Regular physical exercise has many beneficial effects, including antitumor properties, and is associated with a reduced risk of developing hepatocellular carcinoma (HCC). Less is known about the impact of exercise on HCC growth and progression. Here, we investigated the effects of exercise on HCC progression and assessed whether any beneficial effects would be evident under sorafenib treatment and could be mimicked by metformin. American Cancer Institute rats with orthotopic syngeneic HCC derived from Morris Hepatoma-3924A cells were randomly assigned to exercise (Exe) and sedentary groups, or sorafenib±Exe groups or sorafenib±metformin groups. The Exe groups ran on a motorized treadmill for 60 minutes/day, 5 days/week for 4 weeks. Tumor viable area was decreased by exercise, while cell proliferation and vascular density were reduced. Exercise increased the expression of phosphatase and tensin homolog deleted from chromosome 10 and increased the phosphorylation of adenosine monophosphate-activated protein kinase, while the phosphorylation of protein kinase B, S6 ribosomal protein, and signal transducer and activator of transcription 3 were decreased. Transcriptomic analysis suggested major effects of exercise were on nontumoral liver rather than tumor tissue. Exercise demonstrated similar effects when combined with sorafenib. Moreover, similar effects were observed in the group treated with sorafenib+metformin, revealing an exercise-mimicking effect of metformin. Exercise attenuates HCC progression associated with alterations in key signaling pathways, cellular proliferation, tumor vascularization, and necrosis. These beneficial effects are maintained when combined with sorafenib and can be mimicked by metformin. ( 2018;2:607-620).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > CMF
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Saran, Uttara; Guarino, Maria; Rodriguez Navarro, Sarai; St-Pierre, Marie and Dufour, Jean-François

Subjects:

600 Technology
600 Technology > 610 Medicine & health

ISSN:

2471-254X

Publisher:

Wiley

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

01 Oct 2018 10:42

Last Modified:

01 Oct 2018 10:42

Publisher DOI:

10.1002/hep4.1159

PubMed ID:

29761175

BORIS DOI:

10.7892/boris.120174

URI:

https://boris.unibe.ch/id/eprint/120174

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