ABSTRACT
ObjectiveTo explore the mechanism of Liu Junzitang in preventing and treating muscle atrophy in mice with lung cancer cachexia based on the signal transducer and activator of transcription 3（STAT3）/ubiquitin proteasome pathway in vivo. MethodForty C57BL/6 mice aged six weeks were randomly divided into a blank group， a model group， a Liu Junzitang group， an inhibitor group （stattic group），and a Liu Junzitang + inhibitor group （combination group）， with eight mice in each group. The cachectic muscle atrophy model was induced by subcutaneous inoculation of Lewis lung cancer cell line under the right anterior armpit in mice except those in the blank group. On the 8th day after subcutaneous inoculation， the mice in the corresponding groups received Liu Junzitang （9.56 g·kg-1·d-1） by gavage and intraperitoneal injection of stattic ［25 mg·kg-1·（2 d）-1］. After three weeks of drug intervention， the body weight and gastrocnemius muscle weight were recorded. Hematoxylin-eosin （HE） staining was used to observe the pathological changes and cross-sectional area of gastrocnemius muscle fibers in mice. Western blot was used to detect the expression of phosphorylated-STAT3 （p-STAT3）， STAT3， muscle atrophy F-box （MAFbx）， and muscle RING finger protein 1 （MuRF1） in the gastrocnemius muscle. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT3， MAFbx， and MuRF1 in the gastrocnemius muscle. ResultCompared with the blank group， the model group showed lightened body and the gastrocnemius muscle， reduced cross-sectional area of gastrocnemius muscle fibers， and increased protein expression of p-STAT3， STAT3， MAFbx， and MuRF1 and mRNA expression of STAT3， MuRF1， and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the model group， the Liu Junzitang group showed increased body weight， gastrocnemius muscle weight， and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and decreased protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the inhibitor group showed increased body weight and cross-sectional area of gastrocnemius muscle fibers （P<0.05）， and reduced protein expression of p-STAT3， STAT3， MuRF1， MAFbx， and mRNA expression of STAT3 and MAFbx in gastrocnemius muscle （P<0.05）. Compared with the model group， the combination group showed increased body weight and gastrocnemius muscle weight （P<0.05），and decreased protein expression of p-STAT3， STAT3， MuRF1， and mRNA expression of STAT3 and MAFbx in the gastrocnemius muscle （P<0.05）. Compared with the Liu Junzitang group， the stattic group and the combination group showed reduced expression of p-STAT3 protein in the gastrocnemius muscle （P<0.05）. ConclusionLiu Junzitang can prevent and treat muscle atrophy in mice with lung cancer cachexia， and its mechanism may be associated with the protein and mRNA expression related to the STAT3-mediated ubiquitin proteasome pathway.
ABSTRACT
With the emerging cases of tumor is about to exceed 4 million per year in China， tumor prevention and control is also a formidable barrier hitting the world. Overall， an increasing trend of incidence and mortality of tumor in China has been observed in recent years， and the high mortality and low cure rate of tumor have seriously threaten the health of Chinese people， greatly affected the quality of life of patients， greatly reduced the living standard of patients and endangered the physical and mental health of patients. Traditional Chinese medicine（TCM） believes that the etiology of tumor is complex and pathogenesis is variable， which is the result of interaction between internal and external factors. If the treatment is carried out based on syndrome differentiation in time at the beginning when exogenous pathogens act on the human body， so as to prevent the spread of latent pathogen in human body， the occurrence and development of tumor diseases will be significantly reduced. Therefore， the theory of exogenous pathogenic factors and the pathogenesis of tumor need to be further explored. A total of 67 Chinese and English literatures were searched out with key words like external contraction， pathogenic Qi， TCM， tumor and pathogenesis in China National Knowledge Infrastructure （CNKI） and Public Medline （PubMed） databases for reference， so as to discuss the theory of exogenous pathogens and the pathogenesis of tumor comprehensively. The important role of exogenous pathogens in tumor pathogenesis and the significance of TCM in the early prevention and treatment of tumors were emphasized. Exogenous pathogenic factors such as wind， cold， dampness， fire， natural and social factors， diet and living conditions lead to the complexity of the occurrence of tumors. TCM can effectively prevent and intervene in the early stage of tumor onset， contribute to disease prevention and tumor resistance， reduce the occurrence， development and transformation of tumors， and make the clinical medication more effective， more accurate and more targeted， so as not to miss the opportunity for treating tumor， and provide a more clear guidance for clinical treatment of tumors.