Oncotarget

Research Papers:

Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice

Meng-Chuan Chen _, Wen-Lin Hsu, Pa-An Hwang, Yen-Lin Chen and Tz-Chong Chou

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Oncotarget. 2016; 7:51608-51618. https://doi.org/10.18632/oncotarget.9958

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Abstract

Meng-Chuan Chen1,*, Wen-Lin Hsu2,3,*, Pa-An Hwang4, Yen-Lin Chen5, Tz-Chong Chou6,7,8

1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

2School of Medicine, Tzu Chi University, Hualien, Taiwan

3Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

4Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan

5Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

6Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan

7Department of Biotechnology, Asia University, Taichung, Taiwan

8China Medical University Hospital, China Medical University, Taichung, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Tz-Chong Chou, email: [email protected]

Keywords: fucoidan, cancer cachexia, muscle atrophy, chemotherapy, inflammation

Received: November 11, 2015    Accepted: May 17, 2016    Published: June 13, 2016

ABSTRACT

Cancer cachexia is characterized by anorexia, skeletal muscle atrophy, and systemic inflammation. Fucoidan extracted from brown algae exhibits anti-inflammatory and anticancer activities. However, whether fucoidan ameliorates tumour and chemotherapy-induced muscle atrophy and -related cachectic symptoms remains unknown. Compared with mice with bladder cancer treated with chemotherapy alone (TGC group), those treated with a combination of low molecular weight fucoidan (LMWF) and chemotherapy drugs such as gemcitabine and cisplatin (TGCF) showed a significant reduction of body weight loss, muscle atrophy, and intestinal injury and dysfunction. Moreover, myostatin, activin A, and pro-inflammatory cytokine production, FoxO3 expression and activation, NF-κB activation, MuRF-1 and MAFbx/atrogin-1 expression, and proteasome activity in muscle were significantly decreased in the TGCF group compared with the TGC group. In addition, insulin-like growth factor 1 (IGF-1) expression and formation, and IGF-1-regulated mTOR/p70S6k/4EBP-1 protein synthesis signalling were elevated in the TGCF group compared with the TGC group. Taken together, these results suggest that LMWF is a potential agent for preventing cancer cachexia-associated muscle atrophy during chemotherapy. Furthermore, the beneficial effect of LMWF may be attributed to suppressing NF-κB-evoked inflammation, myostatin and activin A production, and subsequent muscle proteolysis, and enhancing IGF-1-dependent protein synthesis.


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