恶性肿瘤恶病质骨骼肌萎缩分子机制研究进展

Progress in the molecular mechanism of skeletal muscle wasting in cancer cachexia

目的:总结国内外对恶性肿瘤恶病质状态下骨骼肌萎缩的分子机制研究进展。方法:应用PubMed和维普期刊资源整合平台,以"恶性肿瘤、恶病质、骨骼肌萎缩、泛素-蛋白酶体途径和自噬信号通路"作为关键词,检索2002-01-01-2013-12-31相关文献。纳入标准:1)恶性肿瘤;2)恶病质;3)骨骼肌萎缩;4)泛素-蛋白酶体途径;5)自噬信号通路。根据纳入标准符合分析的文献33篇。结果:机体在各种刺激下主要通过UPP和ALP降解骨骼肌细胞,ALP在恶病质状态下活性明显升高,UPP可能在恶性肿瘤恶病质中晚期激活。在饥饿和应激等情况下,UPP和ALP可能主要经Akt/PI3K-/mTOR调控;在恶性肿瘤恶病质状态下,FoxO被抑制,骨骼肌萎缩可能主要与NF-κB和p38 MAPK有关。NF-κB能调控E3s转录,并且在Beclin1的基因序列上有相应结合位点;p38MAPK抑制剂SB202190能使E3s及LC3表达下调。结论:对恶性肿瘤恶病质状态下骨骼肌萎缩调控机制的研究将有助于靶向药物的研发,以期改善恶性肿瘤恶病质患者的预后。

OBJECTIVE： To review the progress in the molecular mechanism of skeletal muscle wasting in cancer ca- chexia. METHODS： Use ＂cancer,cachexia,skeletal muscle wasting/atrophy,ubiquitin-proteasome pathway,autophagy-li- sosomal pathway＂ as keywords to search for related papers between Jan. lst,2002 and Dec. 31st,2013 in Pubmed and Vip database. Retrieval criteria ： 1） cancer; 2） cachexia ; 3） skeletal muscle wasting/atrophy; 3 ） UPP; 4） ALP. Thirty-three papers were included. RESULTS= Skeletal muscle wasting takes place mainly through UPP and ALP in various stimuli. ALP ac- tivity is obviously increased in cancer caehexia. UPP may be activated in advanced stage. In starvation or stress,UPP and ALP may be regulated by Akt/PI3 K-FoxO/mTOR. In cancer cachexia, they may both be regulated by NF-κB and p3813 MAPK pathway. NF-~B up-regulates E3s transcription, and has binding site on Beclinl gene. SB202190 down-regulates E3s and LC3 through p38 MAPK inhibition. CONCLUSIONS： Researches on the molecular mechanisms of skeletal muscle wasting in cancer caehexia contribute to the development of targeted drugs and improvement of the patients prognosis.