Esau Peter J, Gittemeier Elizabeth M, Opoku-Acheampong Alexander B, Rollins Korynne S, Baumfalk Dryden R, Poole David C, Musch Timothy I, Behnke Bradley J, Copp Steven W
Department of Kinesiology, Kansas State UniversityManhattan 66506, KS, USA.
Johnson Cancer Research Center, Kansas State UniversityManhattan 66506, KS, USA.
Am J Cancer Res. 2017 Dec 1;7(12):2566-2576. eCollection 2017.
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.
与健康对照者相比,接受雄激素剥夺治疗的前列腺癌患者运动能力降低。我们在一个临床前原位前列腺肿瘤模型中检验了前列腺癌独立降低耐力运动能力的假设。雄性哥本哈根大鼠进行了初始的力竭性跑步机跑步测试。随后向大鼠前列腺注射前列腺肿瘤细胞(R-3327 AT-1,荷瘤,n=9)或载体对照(假手术,n=9),并在术后4周和8周重复跑步机测试。随后在麻醉状态下测量左心室收缩性(LV Δ压力/Δ时间),并解剖心脏和选定的后肢肌肉并称重。各组初始力竭时间无差异(假手术组:28.24±1.26分钟,荷瘤组:28.63±2.49分钟,P=0.90)。术后8周两组的力竭时间均较初始值降低,但荷瘤组(13.25±1.44分钟)明显低于假手术组(21.17±1.87分钟,P<0.01)。在荷瘤组中,LV Δ压力/Δ时间与肿瘤质量显著负相关(-0.71,P<0.05)。术后8周两组体重无差异(P=0.26),但荷瘤组的左心室质量(降低17%,P<0.01)以及选定后肢骨骼肌的质量明显低于假手术组。在荷瘤组中,左心室肌肉质量与前列腺肿瘤质量显著负相关(r=-0.85,P<0.01)。前列腺癌降低了大鼠的耐力运动能力,心脏功能、质量和骨骼肌质量的降低可能在这种损害中起了重要作用。