The effects of doxorubicin and blocking activin receptor 2B ligands in mice [muscle]

Doxorubicin is a widely used and effective anthracycline chemotherapy drug. However, it causes cardiotoxicity and also a few negative effects on skeletal muscle as well. As a result, cancer treatment might actually worsen cancer-induced cachexia and consequently the prognosis of the disease. Inhibiting myostatin/activin signaling is known to increase muscle size. This pathway blockade by soluble activin receptor IIB (sAcvR2B-Fc) has also prolonged survival in cancer, even of animals in which tumor growth is not inhibited. It is not known, however, whether blocking this pathway affects chemotherapy-induced muscle wasting. We found that doxorubicin induces muscle atrophy which is prevented by a blocker for activin receptor 2B ligands (sAcvR2B-Fc). Total RNA obtained from tibialis anterior muscle of mice divided into 3 groups: 1) control (injected with PBS, n= 5), 2) doxorubicin injected alone (Dox, n=5 ), 3) sAcvR2B-Fc administration 48 hours before doxorubicin injection (n=5 ). sActRIIB-Fc, doxorubicin and PBS were injected intraperitoneally. Mice were euthanized 20 hours after doxorubicin or PBS injection.