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Dexamethasone exacerbates cisplatin-induced muscle atrophy
Hiroyasu Sakai1, Minami Kimura2, Yuka Tsukimura1
1Department of Biomolecular Pharmacology, School of Pharmacy, Hoshi University, Shinagawa-ku, Tokyo, Japan.
Clinical and Experimental Pharmacology & Physiology
|August 24, 2018
Summary
Dexamethasone combined with cisplatin worsens chemotherapy-induced muscle atrophy by increasing muscle-specific E3 ubiquitin ligase expression. This combination therapy may exacerbate muscle wasting in cancer patients undergoing treatment.
Area of Science:
- Molecular Biology
- Pharmacology
- Oncology
Background:
- Cisplatin, an anticancer drug, upregulates muscle atrophy genes (MuRF1, Atrogin-1) and promotes muscle wasting.
- Dexamethasone, used for antiemetic therapy with chemotherapy, also upregulates MuRF1 and Atrogin-1 expression.
Purpose of the Study:
- To investigate the combined effects of cisplatin and dexamethasone on muscle atrophy markers.
- To determine if dexamethasone exacerbates cisplatin-induced muscle atrophy in murine models.
Main Methods:
- Murine models and C2C12 myotubes were treated with cisplatin and/or dexamethasone.
- Expression levels of MuRF1, Atrogin-1, myostatin, and IGF-1 were analyzed.
Main Results:
- Dexamethasone enhanced cisplatin-induced upregulation of MuRF1 and Atrogin-1 in skeletal muscles and myotubes.
- Combined treatment exacerbated cisplatin-induced myostatin upregulation and IGF-1 downregulation.
- The combination of cisplatin and dexamethasone significantly worsened muscle atrophy in mice.
Conclusions:
- Combination therapy of cisplatin and dexamethasone exacerbates muscle atrophy.
- This regimen may worsen muscle wasting in cancer patients receiving chemotherapy and antiemetics.
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