Dihydroartemisinin ameliorates skeletal muscle atrophy in the lung cancer cachexia mouse model.

IF 1.3 Journal of cancer research and therapeutics Pub Date : 2024-12-01 Epub Date: 2025-01-10 DOI:10.4103/jcrt.jcrt_140_24
Xin Li, Zhiying Zhu, Keting Wen, Tingting Ling, Hong Huang, Li Qi, Bei Wang
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Abstract

Introduction: Cancer cachexia (CC) is characterized by weight loss with specifically reduced skeletal muscles and adipose tissues in patients with late-stage cancer. Dihydroartemisinin (DHA), an effective antimalarial derivative of artemisinin, has been demonstrated to have anti-inflammatory and antitumor properties.

Materials and methods: This study examined the effects of DHA on the Lewis lung carcinoma (LLC)-induced CC mouse model.

Results: DHA treatment significantly increases tumor-free body weight and food intake but decreases serum interleukin-6 level and tumor weight in CC mice. In addition, DHA treatment relieves muscle atrophy and decreases muscle ring finger 1 (MuRF1) and F-box-only protein 32 (Fbx32) expressions in CC mice. In vitro, DHA reverses the reduction in myotube formation induced by an LLC-conditioned medium and increases Fbx32 expression in C2C12 mouse myotubular cells.

Conclusions: Our study demonstrated that DHA ameliorates the cachectic state and skeletal muscle atrophy in LLC-induced cachectic mouse models, suggesting its therapeutic potential for CC.

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双氢青蒿素改善肺癌恶病质小鼠模型骨骼肌萎缩。
癌症恶病质(CC)的特征是晚期癌症患者体重减轻,骨骼肌和脂肪组织减少。双氢青蒿素(DHA)是青蒿素的有效抗疟疾衍生物,已被证明具有抗炎和抗肿瘤的特性。材料和方法:本研究考察了DHA对Lewis肺癌(LLC)诱导的CC小鼠模型的影响。结果:DHA处理显著增加CC小鼠的无瘤体重和摄食量,降低血清白细胞介素-6水平和肿瘤重量。此外,DHA治疗可以缓解CC小鼠的肌肉萎缩,降低肌肉环指1 (MuRF1)和F-box-only蛋白32 (Fbx32)的表达。在体外,DHA逆转了lc条件培养基诱导的肌小管形成减少,并增加了C2C12小鼠肌小管细胞中Fbx32的表达。结论:我们的研究表明,DHA可以改善llc诱导的病毒质小鼠模型的病毒质状态和骨骼肌萎缩,提示其对CC的治疗潜力。
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