| Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. Cachexia is associated with heart failure and is estimated to be the immediate cause of death in about a third of all cancer patients. The purpose of this study was to investigate cardiac atrophy in the ApcMin/+ mouse model of colorectal cancer. Compared to age matched C57BL/6 (BL6) mice, ApcMin/+ body mass and heart mass were lower at 12 (11.1 +/- 4.5% and 7.6 +/- 2.8%, respectively) and 20-weeks (26.1 +/- 2.5% and 6.0 +/- 3.8%, respectively) of age (P < 0.05). Immunoblot analysis revealed that these changes in mass were accompanied by increased activation of protein kinase B (Akt Thr 473: 74.4 +/- 10.9% and 216.0 +/- 19.6%; Akt Ser 308: 161.6 +/- 31.7% and 367.4 +/- 41.6% at 12- and 20-weeks, respectively, (P < 0.05)), mammalian target of rapamycin (mTOR Ser2448: 23.2 +/- 13.2% and 44.0 +/- 16.4% at 12- and 20-weeks, respectively, (P < 0.05)), 5' adenosine monophosphate-activated protein kinase (AMPK: 19.6 +/- 5.2% and 22.5 +/- 5.5% at 12- and 20-weeks, respectively, (P < 0.05)) and elevated levels of the autophagy regulator beclin1 (4.7 +/- 3.3% and 9.5 +/- 3.0% at 12- and 20-weeks, respectively, (P < 0.05)). No evidence of increased cardiac apoptosis, protein ubiquitination or activation of cardiac caspases or calpains was noted. Taken together, these data suggest that the cardiac atrophy that occurs in the 12- and 20-week old ApcMin/+ mouse is relatively modest compared to that seen with other tumor models [1] and is associated with evidence of increased cardiac autophagy. |
