Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Beta-adrenoceptors attenuate muscle wasting. We hypothesized that specific muscle atrophy signaling pathways and altered metabolism may be attenuated in cancer cachectic animals receiving treatment with the beta₂ agonist formoterol. In diaphragm and gastrocnemius of tumor-bearing rats (intraperitoneal inoculum, 10⁸ AH-130 Yoshida ascites hepatoma cells, 7-day study period) with and without treatment with formoterol (0.3 mg/kg body weight/day/7days, subcutaneous), atrophy signaling pathways (NF-κB, MAPK, FoxO), proteolytic markers (ligases, proteasome, ubiquitination), autophagy markers (p62, beclin-1, LC3), myostatin, apoptosis, muscle metabolism markers, and muscle structure features were analyzed (immunoblotting, immunohistochemistry). In diaphragm and gastrocnemius of cancer cachectic rats, fiber sizes were reduced, levels of structural alterations, atrophy signaling pathways, proteasome content, protein ubiquitination, autophagy, and myostatin were increased, while those of regenerative and metabolic markers (myoD, mTOR, AKT, and PGC-1alpha) were decreased. Formoterol treatment attenuated such alterations in both muscles. Muscle wasting in this rat model of cancer-induced cachexia was characterized by induction of significant structural alterations, atrophy signaling pathways, proteasome activity, apoptotic and autophagy markers, and myostatin, along with a significant decline in the expression of muscle regenerative and metabolic markers. Treatment of the cachectic rats with formoterol partly attenuated the structural alterations and atrophy signaling, while improving other molecular perturbations similarly in both respiratory and limb muscles. The results reported in this study have relevant therapeutic implications as they showed beneficial effects of the beta₂ agonist formoterol in the cachectic muscles through several key biological pathways.

肌肉质量下降和消瘦是包括癌症在内的慢性疾病患者的特征。β-肾上腺素能减弱肌肉消瘦。我们假设，特定肌肉萎缩信号传导途径和代谢改变可以在癌症恶病质的动物接收与所述β处理被衰减₂激动剂福莫特罗。在荷瘤大鼠的diaphragm肌和腓肠肌中（腹膜内接种物，10 ⁸AH-130吉田腹水肝癌细胞，研究期为7天，福莫特罗（0.3 mg / kg体重/天/ 7天，皮下）治疗和不治疗，萎缩信号通路（NF-κB，MAPK，FoxO），蛋白水解标记物（连接酶，蛋白酶体，泛素化），自噬标记（p62，beclin-1，LC3），肌生长抑制素，细胞凋亡，肌肉代谢标记和肌肉结构特征（免疫印迹，免疫组织化学）进行了分析。在癌症恶病质大鼠的横diaphragm膜和腓肠肌中，纤维大小减少，结构改变，萎缩信号通路，蛋白酶体含量，蛋白泛素化，自噬和肌生长抑制素水平增加，而再生和代谢标志物（myoD，mTOR，AKT，和PGC-1alpha）降低。福莫特罗治疗减弱了两块肌肉的这种变化。在这种大鼠的癌症诱发的恶病质模型中，肌肉消瘦的特征在于明显的结构改变，萎缩信号通路，蛋白酶体活性，凋亡和自噬标记物以及肌生长抑制素，以及肌肉再生和代谢标记物的表达显着下降。用福莫特罗治疗恶病质大鼠在一定程度上减弱了结构改变和萎缩信号，同时改善了呼吸和四肢肌肉中的其他分子扰动。这项研究报告的结果显示了β的有益作用，具有相关的治疗意义。以及肌肉再生和代谢标记物的表达显着下降。用福莫特罗治疗恶病质大鼠在一定程度上减弱了结构改变和萎缩信号，同时改善了呼吸和四肢肌肉中的其他分子扰动。这项研究报告的结果显示了β的有益作用，具有相关的治疗意义。以及肌肉再生和代谢标记物的表达显着下降。用福莫特罗治疗恶病质大鼠在一定程度上减弱了结构改变和萎缩信号，同时改善了呼吸和四肢肌肉中的其他分子扰动。这项研究报告的结果显示了β的有益作用，具有相关的治疗意义。₂激动剂福莫特罗通过几种关键的生物途径在恶病质肌肉中发挥作用。