Abstract:
Cancer cachexia-associated muscle wasting as a multifactorial wasting syndrome, is an important factor affecting the long-term survival rate of tumor patients. Photobiomodulation therapy (PBMT) has emerged as a promising tool to cure and prevent many diseases. However, the effect of PBMT on skeletal muscle atrophy during cancer progression has not been fully demonstrated yet. Here, we found PBMT alleviated the atrophy of myotube diameter induced by cancer cells in vitro, and prevented cancer-associated muscle atrophy in mice bearing tumor. Mechanistically, the alleviation of muscle wasting by PBMT was found to be involved in inhibiting E3 ubiquitin ligases MAFbx and MuRF-1. In addition, transcriptomic analysis using RNA-seq and GSEA revealed that PI3K/AKT pathway might be involved in PBMT-prevented muscle cachexia. Next, we showed the protective effect of PBMT against muscle cachexia was totally blocked by AKT inhibitor in vitro and in vivo. Moreover, PBMT-activated AKT promoted FoxO3a phosphorylation and thus inhibiting the nucleus entry of FoxO3a. Lastly, in cisplatin-treated muscle cachexia model, PBMT had also been shown to ameliorate muscle atrophy through enhancing PI3K/AKT pathway to suppress MAFbx and MuRF-1 expression. These novel findings revealed that PBMT could be a promising therapeutic approach in treating muscle cachexia induced by cancer.
摘要:
癌症恶病质相关的肌肉消瘦是一种多因素消瘦综合征,是影响肿瘤患者远期生存率的重要因素。光生物调节疗法(PBMT)已成为治愈和预防许多疾病的有希望的工具。然而,PBMT对癌症进展过程中骨骼肌萎缩的影响尚未得到充分证实.这里,我们发现PBMT在体外减轻了癌细胞诱导的肌管直径萎缩,并预防荷瘤小鼠的癌症相关肌肉萎缩。机械上,发现PBMT减轻肌肉萎缩与抑制E3泛素连接酶MAFbx和MuRF-1有关。此外,使用RNA-seq和GSEA的转录组学分析显示PI3K/AKT途径可能参与PBMT预防的肌肉恶病质。接下来,我们表明PBMT对肌肉恶病质的保护作用在体外和体内被AKT抑制剂完全阻断。此外,PBMT激活的AKT促进FoxO3a磷酸化并因此抑制FoxO3a的核进入。最后,在顺铂治疗的肌肉恶病质模型中,PBMT还显示通过增强PI3K/AKT途径以抑制MAFbx和MuRF-1表达来改善肌肉萎缩。这些新发现揭示PBMT可能是治疗癌症引起的肌肉恶病质的有希望的治疗方法。