Prostate cancer reduces endurance exercise capacity in association with reductions in cardiac and skeletal muscle mass in the rat.

Abstract

Exercise capacity is reduced in prostate cancer patients concurrently treated with androgen deprivation therapy compared to healthy counterparts. We tested the hypothesis that prostate cancer independently reduces endurance exercise capacity in a preclinical orthotopic prostate tumor model. Male Copenhagen rats performed an initial treadmill running test to exhaustion. The rats' prostates were subsequently injected with either prostate tumor cells (R-3327 AT-1, tumor bearing, n=9) or vehicle control (sham, n=9) and the treadmill tests were repeated four and eight weeks post-surgery. Left ventricle contractility (LV Δpressure/Δtime) was subsequently measured under anesthesia and the heart and select hindlimb muscles were dissected and weighed. Initial times to exhaustion were not different between groups (sham: 28.24±1.26, tumor bearing: 28.63±2.49 min, P=0.90). Time to exhaustion eight weeks post-surgery was reduced compared to initial values for both groups but was significantly lower in the tumor bearing (13.25±1.44 min) versus the sham (21.17±1.87 min, P<0.01) group. Within the tumor bearing group, LV Δpressure/Δtime was significantly negatively correlated with tumor mass (-0.71, P<0.05). Body mass at eight weeks post-surgery was not different between groups (P=0.26) but LV mass (↓17%, P<0.01), as well as the mass of select hindlimb skeletal muscles, was significantly lower in the tumor bearing versus sham group. Within the tumor bearing group, LV muscle mass was significantly negatively correlated with prostate tumor mass (r=-0.85, P<0.01). Prostate cancer reduced endurance exercise capacity in the rat and reductions in cardiac function and mass and skeletal muscle mass may have played an important role in this impairment.