| RRC ID |
54071
|
| 著者 |
Sakai H, Kimura M, Tsukimura Y, Yabe S, Isa Y, Kai Y, Sato F, Kon R, Ikarashi N, Narita M, Chiba Y, Kamei J.
|
| タイトル |
Dexamethasone exacerbates cisplatin-induced muscle atrophy.
|
| ジャーナル |
Clin Exp Pharmacol Physiol
|
| Abstract |
Dexamethasone for antiemetic therapy is typically administered with anticancer drugs such as cisplatin. We previously reported that cisplatin upregulates the muscle-specific E3 ubiquitin ligase genes, namely muscle ring-finger protein 1 (MuRF1) and atrophy gene-1 (atrogin-1), and promotes muscle atrophy in mice. It is well known that dexamethasone causes upregulation of MuRF1 and Atrogin-1 expression in skeletal muscles. Although it is speculated that a combination of dexamethasone and cisplatin worsens muscle atrophy, there are no reports based on research. We thereby investigated the effects of cisplatin and dexamethasone, alone or in combination, on the expression of MuRF1 and Atrogin-1 in murine skeletal muscles and C2C12 myotubes. Mice were intraperitoneally injected with cisplatin or the vehicle control once daily for 4 days. Dexamethasone or the vehicle control was subcutaneously administered 30 minutes prior to the administration of cisplatin. Dexamethasone enhanced MuRF1 and Atrogin-1 gene expression upregulated by cisplatin in murine quadriceps muscles and C2C12 myotubes. Cisplatin-caused upregulation of myostatin and downregulation of IGF-1 gene expression were also enhanced by co-administration of dexamethasone in murine quadriceps muscles and C2C12 myotubes. This study shows that the combination treatment of cisplatin and dexamethasone exacerbated muscle atrophy in mice. Therefore, this treatment regimen might exacerbate muscle atrophy in cancer patients.
|
| 巻・号 |
46(1)
|
| ページ |
19-28
|
| 公開日 |
2019-1-1
|
| DOI |
10.1111/1440-1681.13024
|
| PMID |
30137654
|
| MeSH |
Animals
Body Weight / drug effects
Cisplatin / adverse effects*
Dexamethasone / adverse effects*
Drug Synergism
Gene Expression Regulation / drug effects
Mice
Muscle Fibers, Skeletal / drug effects
Muscle Fibers, Skeletal / metabolism
Muscle Fibers, Skeletal / pathology
Muscle Proteins / genetics
Muscular Atrophy / chemically induced*
Muscular Atrophy / genetics
Muscular Atrophy / pathology
SKP Cullin F-Box Protein Ligases / genetics
Tripartite Motif Proteins / genetics
Ubiquitin-Protein Ligases / genetics
|
| IF |
2.456
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
C2C12(RCB0987) |
