Abstract
Patients with cancer often experience muscle atrophy, which worsens their prognosis. Decreased muscle regenerative capacity plays an important role in the complex processes involved in muscle atrophy. Administration of cisplatin, a cancer chemotherapeutic agent, has been implicated as a cause of muscle atrophy. In this study, we examined whether cisplatin affects the differentiation of myoblasts into myotubes. We treated C2C12 myoblasts with a differentiation medium containing cisplatin and its vehicle during for 8 days and observed the changes in the expression of myosin heavy chain (MyHC) and myogenin in the myoblasts. Cisplatin was injected in mice for 4 consecutive days; on Day 5, the mice quadriceps muscles were sampled and examined. The expression of MyHCs increased and that of myogenin decreased after cisplatin treatment. The secretion of acidic cysteine-rich proteins (e.g., Sparc proteins) reportedly promotes C2C12 myoblast differentiation. Therefore, we investigated the Sparc family gene expression during myogenesis in C2C12 myoblasts after cisplatin treatment. Of all the genes investigated, Sparc-like protein 1 (Sparcl1) expression was significantly suppressed by cisplatin on Days 4-8. Simultaneous treatment with recombinant mouse Sparcl1 almost inhibited the cisplatin-induced suppression of total MyHC and myogenin protein levels. Moreover, Sparcl1 expression decreased in the skeletal muscles of mice, leading to cisplatin-induced muscle atrophy. Our results suggest that cisplatin-induced myogenesis suppression causes muscle atrophy and inhibits the expression of Sparcl1, which promotes C2C12 cell differentiation during myogenesis.