Formoterol May Activate Rat Muscle Regeneration During Cancer Cachexia

Abstract

PURPOSE: The development of cancer cachexia is the most common manifestation of advanced malignant disease. METHOD: The effects on muscle regeneration of β2-adrenoceptor agonist formoterol (0.3 mg/kg) were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). RESULTS: Administration of formoterol results in a significant increase in the mass and protein content of tibialis muscle in tumour-bearing-rats. This increase is associated with a decreased myogenin mRNA content together with an increased Pax-7 gene expression. Bupivacaine treatment by local injection results in an important reduction in tibialis weight together with significant increases in Pax-7, myogenin and MyoD gene expression. Formoterol treatment in bupivacaine-treated rats results in significant increases in Pax-7 together with significant decreases in myogenin mRNA content, suggesting that this β2-agonist is favouring muscle regeneration by stimulating the proliferation of satellite cells. Altogether, the data reinforce the potential role of formoterol in the treatment of muscle wasting diseases.

Formoterol in the treatment of experimental cancer cachexia: effects on heart function

“…Formoterol is able to ameliorate muscle wasting in tumour-bearing rats through different mechanisms that include decreased protein degradation [ 26 ], increased protein synthesis, decreased apoptosis [ 26 ] and increased muscle regeneration [ 30 ]. Formoterol also reduces oxidative stress associated with muscle wasting [ 31 ].…”

Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action

“…Furthermore, formoterol administration in bupivacaine-treated rats ameliorates muscle wasting by increasing Pax7 and decreasing myogenin mRNA content which further stimulates satellite cell proliferation and favors muscle regeneration. In addition, formoterol can induce mitochondrial biogenesis to prevent dexamethasone induced atrophy [120,121]. Beneficial effect of formoterol was also observed under both cancer cachexia (Yoshida AH-130 ascites tumor bearing rat) and sarcopenic conditions.…”

Formoterol and cancer muscle wasting in rats: Effects on muscle force and total physical activity

“…Thirdly, at least in vitro formoterol increased protein synthesis in skeletal muscle (19). Notably, these effects of the β 2 -agonist appear to be associated with an increased muscle regeneration capacity (25).…”