AuPS Logo
Previous Next PDF

Myostatin inhibition attenuates atrophy and loss of muscle function in mice with cancer cachexia

K.T. Murphy, A. Chee and G.S. Lynch, Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, VIC 3010, Australia.

Cancer cachexia describes the progressive skeletal muscle wasting and weakness in many cancer patients. Cancer cachexia impairs mobility, causes severe fatigue, and accounts for >20% of cancer-related deaths. We tested the hypothesis that antibody-directed myostatin inhibition would attenuate the atrophy and loss of function in skeletal muscles of tumour-bearing mice. Twelve week old C57BL/6 mice received a subcutaneous injection of saline (Control) or 7.5×105 Lewis Lung Carcinoma (LLC) tumour cells. One week later, mice began once-weekly injections of saline (Control, n=12; LLC, n=9) or a mouse chimera of anti-human myostatin antibody (PF-354, 10 mg/kg/week, Pfizer Global Research and Development, Groton; USA; LLC+PF-354, n=11), which continued for 5 weeks. Compared with controls, LLC mice had an 8-10% lower muscle mass (P<0.05) which was prevented with PF-354 (P>0.20). Peak tetanic in situ force production of tibialis anterior (TA) muscles of LLC mice was reduced by 8% (P<0.05), but this deficit was attenuated with PF-354 treatment (P>0.05). PF-354 increased the cross-sectional area (CSA) of Type IIx/b fibres in TA muscle from LLC mice by 12% (P<0.05), but there was no difference between groups in CSA of Type IIa fibres (P=0.56). Apoptosis in cross-sections of TA muscle from LLC mice was increased by 140% (P<0.05), but this increase was prevented with PF-354 treatment (P>0.05). Antibody-directed myostatin inhibition attenuated the skeletal muscle atrophy and loss of muscle force-producing capacity in a murine model of cancer cachexia, in part by reducing apoptosis. These findings highlight the therapeutic potential of myostatin inhibition for cancer cachexia.