肿瘤恶病质骨骼肌消耗机制的研究进展

Progress in Mechanism of Muscle Wasting in Cachexia

目的:从泛素–蛋白酶体系统(UPS)与自噬–溶酶体系统(ALS)探讨肿瘤恶病质骨骼肌消耗的机制及其上游信号通路,从而为恶病质发生的防治研究提供依据。方法:检索Medline相关文献,以“肿瘤恶病质、骨骼肌消耗”等为关键词,检索1971-01~2013-06的相关文献,共检索到英文文献898条。纳入标准:1) 近10年相关文献;2) 与骨骼肌消耗的信号通路及效应因子相关。剔除标准1) 与肿瘤恶病质无关的骨骼肌消耗;2) 与UPS或ALS无关的信号通路及效应因子。符合纳入标准的英文文献87条,根据剔除标准剔除英文文献31条,最后纳入分析25篇文献。结果:在肿瘤恶病质的发生发展过程中,多种效应因子通过调节UPS与ALS两大系统的作用,促进了蛋白质的降解,进而造成骨骼肌的消耗。结论:UPS与ALS为参与肿瘤恶病质骨骼肌消耗的两大重要系统,如果可以阻断造成UPS与ALS两大系统交互作用异常放大的通路,肿瘤恶病质的发生就能够得以控制,进而改善肿瘤患者的生存质量、延长其生存期,甚至为肿瘤患者的康复带来一线希望。

Objective: This article summarized the progress in study of muscle wasting in cancer cachexia. It inquired into the mechanism and up-stream signaling cascades of muscle wasting in cancer ca-chexia from ubiquitin-proteasome and autophagy-lysosomal systems perspective, laying the foundation of study in prophylaxis and treatment of cancer cachexia. Methods: Using Medline to search literature about cancer cachexia and muscle wasting from Jan. 1971 to Jun. 2013, and getting 898 pieces of literature in total. Inclusion Criteria: 1) relevant literature in latest decade;2) related to the signaling cascades and effective factors of muscle wasting. Exclusion Criteria: 1) muscle wasting irrelated to cancer cachexia;2) signaling cascades and effective factors irrelated to UPS or ALS. Literatures meeting inclusion criteria are 87 pieces, and literatures eliminated ac-cording to exclusion criteria are 31 pieces. Literatures analyzed eventually are 25 pieces. Results: Multiple factors promote the muscle wasting by stimulating the protein-degradation pathways which are UPS and ALS, leading to the onset and development of cancer. Conclusions: UPS and ALS are two highly effective protein-degradation pathways correlative to cachexia. If the signaling cascades leading to the hyperactivities of UPS and ALS can be blocked, the occurrence of cachexia will be prevented, and then the quality of life will be improved, the survival period will be prolonged, and it even will bring a glimmer of hope for recovery of cancer patients.