Kumar Neha, Davis Logan R, Aune Gregory J, Rivas Paul, Kumar Addanki P, Patel Darpan I
School of Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas, United States.
Greehy Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States.
J Appl Physiol (1985). 2025 Aug 1;139(2):465-472. doi: 10.1152/japplphysiol.00039.2025. Epub 2025 Jul 10.
Cytotoxic treatments pose a significant cardiotoxic risk to men with prostate cancer (PCa). Exercise has been found to prevent cardiotoxicities. Previous work from our group has also identified the chemopreventative effects of phellodendron amurense (PhAm). We therefore aimed to compare the effectiveness of exercise ± PhAm on cardiac function in a transgenic PCa mouse model. A 12-wk, four-arm, randomized controlled study was performed. Twenty-four transgenic adenocarcinoma of the mouse prostate mice were randomly assigned to either the control, exercise, PhAm, or exercise with PhAm (ExPhAm) treatment groups. Mice assigned to exercise were given continuous access to a running wheel. PhAm groups consumed a diet enriched with PhAm at 600 mg/kg. Control animals maintained a normal diet and activity. Pre-post echocardiography was performed to measure heart rate, interventricular septum (IVS) thickness, left ventricle (LV) internal diameter, LV volume, ejection fraction, fractional shortening, and left ventricle mass. Exercise, PhAm, and the combination were able to protect against an increase in end-diastolic and end-systolic LV mass ( = 0.003; = 0.006, respectively). Although not significant, the LV/body mass was markedly higher in the exercise group (+4.5%) and combination (+1.1%) compared with the PhAm (-4.2%) and control groups (-10.3%). Exercise and ExPhAm also protected against increases in IVS thickening, whereas an increase was found in both the PhAm and control groups ( < 0.05). The results of our study suggest that exercise is the driving factor in promoting cardiac health in PCa and can prevent cardiotoxicities associated with the tumor burden. Exercise is effective in preventing significant left ventricular hypertrophy (when evaluated using relative wall thickness) and promoting a younger mouse phenotype. Exercise was the driving force in the Ex and ExPhAm groups. This resulted in the prevention of significant left ventricular hypertrophy and promotion of a younger mouse phenotype.
细胞毒性治疗对前列腺癌（PCa）男性患者构成重大的心脏毒性风险。已发现运动可预防心脏毒性。我们团队之前的研究还确定了黄柏（PhAm）的化学预防作用。因此，我们旨在比较运动±黄柏对转基因PCa小鼠模型心脏功能的有效性。进行了一项为期12周的四臂随机对照研究。将24只小鼠前列腺转基因腺癌小鼠随机分配至对照组、运动组、黄柏组或运动加黄柏（ExPhAm）治疗组。分配至运动组的小鼠可随时使用跑步轮。黄柏组食用富含600 mg/kg黄柏的饮食。对照动物维持正常饮食和活动。在实验前后进行超声心动图检查，以测量心率、室间隔（IVS）厚度、左心室（LV）内径、LV容积、射血分数、缩短分数和左心室质量。运动、黄柏及其组合均能够防止舒张末期和收缩末期LV质量增加（分别为P = 0.003；P = 0.006）。虽然差异不显著，但与黄柏组（-4.2%）和对照组（-10.3%）相比，运动组（+4.5%）和联合组（+1.1%）的LV/体重明显更高。运动和ExPhAm还可防止IVS增厚增加，而黄柏组和对照组均出现增厚增加（P < 0.05）。我们的研究结果表明，运动是促进PCa患者心脏健康的驱动因素，可预防与肿瘤负荷相关的心脏毒性。运动在预防显著的左心室肥厚（使用相对壁厚度评估时）和促进年轻小鼠表型方面有效。运动是Ex组和ExPhAm组的驱动力。这导致预防了显著的左心室肥厚并促进了年轻小鼠表型。
