PDF(Pubmed)
Abstract：
Cancer cachexia is a multifactorial condition that contributes to the death of about 20% of cancer patients. It has the potential to cause weight loss, reduction in muscle mass, and loss of fat tissue, significantly lowering the quality of life. Currently, there are no approved drugs for cancer cachexia. Here, we have explored the possible impact of brassinin (BSN) on cancer cachexia under in vitro and in vivo settings. After differentiation, C2C12 and 3T3-L1 cells were incubated with colorectal carcinoma cells conditioned media or BSN. For preclinical studies, mice were injected with HT-29 cells followed by intraperitoneal administration of BSN, and muscle and adipose tissues were evaluated by Western blotting and hematoxylin and eosin staining. BSN effectively suppressed muscle atrophy by down-regulating the levels of Muscle RING-finger protein-1 and Atrogin-1, while also increasing the expression of myosin heavy chain in cachexia-induced-C2C12 myotubes. The induction of adipogenesis by BSN prevented adipocyte atrophy in cachexia-induced 3T3-L1 adipocytes. We also noted that BSN disrupted the interaction between COX-2 and signaling transducer and activator of transcription 3 (STAT3) promoter, leading to down-regulation of STAT3 activation. Moreover, it was found that BSN inhibited weight loss in mice and demonstrated anti-cachexic effects. Overall, our observations indicate that BSN can attenuate cancer cachexia through diverse mechanisms.
摘要：
癌症恶病质是一种多因素疾病，导致约20％的癌症患者死亡。它有可能导致体重减轻，肌肉质量减少，和脂肪组织的流失，显著降低生活质量。目前,目前还没有批准的癌症恶病质药物。这里,我们已经探讨了在体外和体内环境下，油菜素（BSN）对癌症恶病质的可能影响。分化后,将C2C12和3T3-L1细胞与结肠直肠癌细胞条件培养基或BSN一起孵育。对于临床前研究，小鼠注射HT-29细胞，然后腹膜内注射BSN，通过蛋白质印迹和苏木精和伊红染色评估肌肉和脂肪组织。BSN通过下调肌肉RING-finger蛋白-1和Atrogin-1的水平有效抑制肌肉萎缩，同时还增加恶病质诱导的C2C12肌管中肌球蛋白重链的表达。BSN诱导脂肪生成可防止恶病质诱导的3T3-L1脂肪细胞中的脂肪细胞萎缩。我们还注意到，BSN破坏了COX-2与信号转导子和转录激活因子3（STAT3）启动子之间的相互作用，导致STAT3激活下调。此外，发现BSN抑制小鼠体重减轻并表现出抗恶病质作用。总的来说,我们的观察结果表明,BSN可以通过多种机制减轻癌症恶病质.
