McAllister Heart Institute and Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC.
School of Sport and Exercise Science, and the University of Northern Colorado Cancer Rehabilitation Institute, University of Northern Colorado, Greeley, CO.
Med Sci Sports Exerc. 2018 Jun;50(6):1169-1176. doi: 10.1249/MSS.0000000000001544.
Cancer has been shown to negatively stimulate autophagy, leading to a decline in cardiac function. Although exercise is cardioprotective, its influence over autophagy-mediated tumor growth and cardiac function are not well defined.
This study aimed to determine the effect of exercise on tumor morphology and cardiac function.
Fisher 344 rats (n = 28) were assigned to one of four groups: 1) sedentary non-tumor bearing (SED), 2) sedentary tumor bearing (SED + T), 3) wheel run non-tumor bearing (WR), or 4) wheel run tumor bearing (WR + T). Rats remained sedentary or exercised for 6 wk. At week 4, rats in tumor groups were inoculated with MatBIII tumor cells. At week 6, cardiac function was measured.
SED + T animals exhibited significantly lower left ventricular developed pressure when compared with SED, WR, and WR + T (P < 0.05). This coincided with a significant increase in cardiac autophagy (increased LC3-II) in SED + T animals when compared with SED, WR, and WR + T (P < 0.05). Furthermore, SED + T hearts showed a significant increase in β-myosin heavy chain expression versus nontumor groups (P < 0.05). Tumor mass was significantly larger (P < 0.001) in SED + T animals when compared with WR + T animals, which was accompanied by a significant increase in tumor LC3-II protein expression (P < 0.05).
Nonexercised tumor-bearing rats showed severe cardiac dysfunction and excessive, maladaptive autophagy in the heart and tumors. Voluntary exercise preserved cardiac function and attenuated the autophagic response in heart and tumor tissues. This preservation may be related to the reduced tumor growth in aerobically exercised rats, to the improved regulation of autophagy by exercise, or both.
癌症已被证明会抑制自噬，从而导致心脏功能下降。虽然运动对心脏有保护作用，但它对自噬介导的肿瘤生长和心脏功能的影响尚不清楚。
本研究旨在确定运动对肿瘤形态和心脏功能的影响。
将 28 只 Fisher 344 大鼠分为四组：1）安静非肿瘤组（SED），2）安静肿瘤组（SED+T），3）轮跑非肿瘤组（WR）或 4）轮跑肿瘤组（WR+T）。大鼠保持安静或运动 6 周。在第 4 周，肿瘤组大鼠接种 MatBIII 肿瘤细胞。在第 6 周，测量心脏功能。
SED+T 动物的左心室发展压明显低于 SED、WR 和 WR+T（P<0.05）。这与 SED+T 动物的心脏自噬（增加 LC3-II）明显增加一致，与 SED、WR 和 WR+T 相比（P<0.05）。此外，SED+T 心脏的β-肌球蛋白重链表达明显高于非肿瘤组（P<0.05）。SED+T 动物的肿瘤质量明显大于 WR+T 动物（P<0.001），并伴有肿瘤 LC3-II 蛋白表达的显著增加（P<0.05）。
未运动的肿瘤荷瘤大鼠表现出严重的心脏功能障碍和心脏及肿瘤组织中过度的适应性自噬。自愿运动可保持心脏功能，减轻心脏和肿瘤组织中的自噬反应。这种保护可能与有氧运动大鼠肿瘤生长减少、运动对自噬的调节改善有关，或者两者兼而有之。
