Baumfalk Dryden R, Opoku-Acheampong Alexander B, Caldwell Jacob T, Butenas Alec L E, Horn Andrew G, Kunkel Olivia N, Copp Steven W, Ade Carl J, Musch Timothy I, Behnke Bradley J
Department of Kinesiology, Kansas State University Manhattan 66506, Kansas, USA.
Johnson Cancer Research Center, Kansas State University Manhattan 66506, Kansas, USA.
Am J Transl Res. 2021 Jan 15;13(1):197-209. eCollection 2021.
Recent evidence suggests prostate cancer independent of treatment has atrophic effects on whole heart and left ventricular (LV) masses, associated with reduced endurance exercise capacity. In a pre-clinical model, we tested the hypothesis that high-intensity training could prevent cardiac atrophy with prostate cancer and alter cardiac protein degradation mechanisms.
Dunning R-3327 AT-1 prostate cancer cells (1×10) were injected into the ventral prostate lobe of 5-6 mo immunocompetent Copenhagen rats (n=24). These animals were randomized into two groups, tumor-bearing exercise (TBEX, n=15) or tumor bearing sedentary (TBS, n=9). Five days after surgery, TBEX animals began exercise on a treadmill (25 m/min, 15° incline) for 45-60 min/day for 18±2 days. Pre-surgery (Pre), and post-exercise training (Post) echocardiographic evaluation (Vivid S6, GE Health Care), using the parasternal short axis view, was used to examine ventricle dimensions. Markers of protein degradation (muscle atrophy F-box, Cathepsin B, Cathepsin L) in the left ventricle were semi-quantified via Western Blot.
There were no significant differences in tumor mass between groups (TBEX 3.4±0.7, TBS 2.8±0.6 g, P=0.3), or body mass (TBEX 317±5, TBS 333±7 g, P=0.2). Heart-to-body mass ratio was lower in TBS group compared to TBEX (2.3±0.1 vs. 2.5±0.1 mg/g, P<0.05). LV/body mass ratio was also lower in the TBS group (1.6±0.1 vs. 1.8±0.1 mg/g, P<0.05). From Pre-Post, TBEX had significant increases in SV (~20% P<0.05) whereas TBS had no significant change. There were no significant differences between groups for markers of protein degradation.
This study suggests that high-intensity exercise can improve LV function and increase LV mass concurrent with prostate cancer development, versus sedentary counterparts. Given cardiac dysfunction often manifests with conventional anti-cancer treatments, a short-term high-intensity training program, prior to treatment, may improve cardiac function and fatigue resistance in cancer patients.
最近的证据表明，与治疗无关的前列腺癌对全心和左心室（LV）质量具有萎缩性影响，并伴有耐力运动能力下降。在一个临床前模型中，我们检验了高强度训练可以预防前列腺癌导致的心脏萎缩并改变心脏蛋白质降解机制这一假设。
将邓宁R-3327 AT-1前列腺癌细胞（1×10）注射到5-6个月龄具有免疫能力的哥本哈根大鼠（n = 24）的腹侧前列腺叶中。这些动物被随机分为两组，即荷瘤运动组（TBEX，n = 15）和荷瘤久坐组（TBS，n = 9）。手术后5天，TBEX组动物开始在跑步机上运动（25米/分钟，15°坡度），每天45 - 60分钟，持续18±2天。术前（Pre）和运动训练后（Post）采用胸骨旁短轴视图，通过超声心动图评估（Vivid S6，GE医疗）来检查心室大小。通过蛋白质印迹法对左心室中蛋白质降解标记物（肌肉萎缩F盒蛋白、组织蛋白酶B、组织蛋白酶L）进行半定量分析。
两组之间肿瘤质量（TBEX组3.4±0.7克，TBS组2.8±0.6克，P = 0.3）或体重（TBEX组317±5克，TBS组333±7克，P = 0.2）均无显著差异。与TBEX组相比，TBS组的心脏与体重比更低（2.3±0.1对2.5±0.1毫克/克，P < 0.05）。TBS组的左心室与体重比也更低（1.6±0.1对1.8±0.1毫克/克，P < 0.05）。从术前到术后，TBEX组的每搏输出量显著增加（约20%，P < 0.05），而TBS组无显著变化。两组之间蛋白质降解标记物无显著差异。
本研究表明，与久坐的对照组相比，高强度运动可在前列腺癌发展过程中改善左心室功能并增加左心室质量。鉴于传统抗癌治疗常伴有心脏功能障碍，在治疗前进行短期高强度训练计划可能会改善癌症患者的心脏功能和抗疲劳能力。
