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Effect of acute treadmill exercise on cisplatin-induced muscle atrophy in the mouse

  • Muscle physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Cisplatin, a platinum-based anti-cancer drug, is one of the most effective broad-spectrum anti-cancer agents used against various cancers. It has been recently suggested that low skeletal muscle mass is predictive of mortality in patients with cancer. Although several molecules produced by the actual tumor itself contribute to skeletal muscle impairment, we recently suggested that the administration of cisplatin could increase levels of muscle RING finger-1 (MuRF1) and atrogin-1, possibly leading to muscle atrophy in the mouse. Exercise is an important factor that induces muscle protein synthesis and muscle hypertrophy by enhancing the positive effects of the Akt/mTOR/p70S6 kinase pathway. In the present study, we therefore investigated the effect of treadmill exercise on cisplatin-induced muscle atrophy. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for four consecutive days. On day 4, the quadriceps and gastrocnemius muscles were isolated from the mice. The animals in the treadmill exercise groups were forced to run on a motorized treadmill for 20 min once a day for 9 days. In addition to muscle mass, the decrease in myofiber diameter associated with cisplatin administration was significantly restored by treadmill exercise. This exercise also significantly attenuated cisplatin-induced upregulation of MuRF1 and atrogin-1 in quadriceps and gastrocnemius muscle. The decreased Akt, p70S6 kinase, and Foxo3a phosphorylation observed with cisplatin treatment was significantly recovered by treadmill exercise in both the muscles. In the present study, myostatin (Mstn) gene expression, upregulated by cisplatin administration, was also attenuated by treadmill exercise. These findings suggest that treadmill exercise could attenuate cisplatin-induced muscle atrophy, at least partially, and could improve prognosis.

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Acknowledgments

This work was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S1411019) and by KAKENHI (15K18880), a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Hiroyasu Sakai, Minami Kimura, Yosuke Isa, Saori Yabe, Akihide Maruyama, Yukari Tsuruno, Yuki Kai, Fumiaki Sato & Tetsuro Yumoto

  2. Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Yoshihiko Chiba

  3. Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Minoru Narita

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  1. Hiroyasu Sakai
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Contributions

HS, MK, YI, SY, AM, YT, and YK performed the experiments and analyzed the data. FS, TY, YC, and MN provided technical support. HS and MN initiated and supervised the study. HS and MN designed experiments and analyzed data. HS and YC wrote the manuscript.

Corresponding author

Correspondence to Hiroyasu Sakai.

Ethics declarations

All experiments were approved by the Animal Care Committee at Hoshi University (Tokyo, Japan).

Competing interests

The authors declare that they have no competing interests.

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Sakai, H., Kimura, M., Isa, Y. et al. Effect of acute treadmill exercise on cisplatin-induced muscle atrophy in the mouse. Pflugers Arch - Eur J Physiol 469, 1495–1505 (2017). https://doi.org/10.1007/s00424-017-2045-4

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  • DOI: https://doi.org/10.1007/s00424-017-2045-4

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