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八宝丹通过抑制 IL-6/STAT3 信号通路缓解小鼠癌性恶病质。

Babao Dan Alleviates Cancer Cachexia in Mice Via Inhibiting IL-6/STAT3 Signaling Pathway.

机构信息

Fujian Key Laboratory of Integrative Medicine on Geriatrics, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.

出版信息

Integr Cancer Ther. 2023 Jan-Dec;22:15347354231168369. doi: 10.1177/15347354231168369.

Abstract

BACKGROUND

Cancer cachexia is a common but severe condition that causes muscle wasting, body weight loss, and progressive functional impairment, affecting over 50% of cancer patients. Currently, there are no effective treatments that can alleviate cachexia, and hence the discovery of new therapeutics that can effectively prevent or even reverse cancer cachexia is crucial. Babao Dan (BBD) is a Traditional Chinese Medicine (TCM) formula that has been used clinically in combating various cancers, however, its therapeutic potential in alleviating cancer cachexia remains unexplored. Our current study aims to determine the anti-cachectic effects of BBD treatment in alleviating cancer cachexia, as well as determining the underlying mechanisms involved.

METHODS

Mouse models of cancer cachexia were induced via implantation of CT26 colon adenocarcinoma cells, and the anti-cachectic effects and mechanisms of BBD were determined via examinations of body weight and muscle mass, as well as serum and muscle markers of cachexia and muscle atrophy.

RESULTS

CT26 tumor implantation reduced in the rapid occurrence of cancer cachexia characterized by marked reductions in body weight and muscle mass, functional decrease in muscle function and accelerated deaths. BBD administration not only demonstrated robust anti-cachectic ability via preventing decreases in body weight, muscle mass, and muscle atrophy, but also markedly prolonged survival. The effects of BBD in alleviating cancer cachexia and its associated adverse effects were due to its ability in preventing the activation of IL-6/STAT3 signaling post-CT26 tumor implantation.

CONCLUSION

Our findings demonstrated the robust ability of BBD in preventing cancer cachexia and alleviating the main cachexia-induced symptoms as well as prolonging survival via inhibiting activation of IL-6/STAT3 signaling pathway. Therefore, our study demonstrating the strong anti-cachectic effects of BBD in mice may provide a theoretical basis for the use of BBD as a safe and effective drug in the treatment of cancer cachexia.

摘要

背景

癌症恶病质是一种常见但严重的病症,可导致肌肉消耗、体重减轻和进行性功能障碍,影响超过 50%的癌症患者。目前,尚无有效的治疗方法可以缓解恶病质,因此发现能够有效预防甚至逆转癌症恶病质的新疗法至关重要。八宝丹(BBD)是一种中药配方,已在临床上用于治疗各种癌症,但它在缓解癌症恶病质方面的治疗潜力尚未得到探索。我们目前的研究旨在确定 BBD 治疗缓解癌症恶病质的抗恶病质作用,并确定相关的作用机制。

方法

通过植入 CT26 结肠腺癌细胞诱导癌症恶病质小鼠模型,通过检查体重和肌肉质量,以及血清和肌肉恶病质和肌肉萎缩标志物,确定 BBD 的抗恶病质作用和机制。

结果

CT26 肿瘤植入导致癌症恶病质快速发生,表现为体重和肌肉质量明显下降,肌肉功能下降和加速死亡。BBD 给药不仅通过防止体重、肌肉质量和肌肉萎缩的减少表现出强大的抗恶病质能力,而且还显著延长了生存时间。BBD 缓解癌症恶病质及其相关不良影响的作用归因于其在 CT26 肿瘤植入后预防 IL-6/STAT3 信号通路激活的能力。

结论

我们的研究结果表明,BBD 具有强大的预防癌症恶病质的能力,可缓解主要恶病质引起的症状,并通过抑制 IL-6/STAT3 信号通路的激活延长生存时间。因此,我们在小鼠中证明 BBD 具有强大的抗恶病质作用的研究结果可能为将 BBD 作为治疗癌症恶病质的安全有效药物提供理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7756/10126781/08aef7fcc7f6/10.1177_15347354231168369-fig1.jpg

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