PMID- 27493875 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160805 LR - 20220330 IS - 2190-5991 (Print) IS - 2190-6009 (Electronic) IS - 2190-5991 (Linking) VI - 7 IP - 2 DP - 2016 May TI - Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling. PG - 225-32 LID - 10.1002/jcsm.12054 [doi] AB - BACKGROUND: Cachexia has a devastating impact on survival and quality of life for many cancer patients and contributes to nearly one-third of all cancer deaths; also, it is associated with poor responses to chemotherapy and survival. A better understanding of the underlying mechanisms of cancer-associated cachexia (CAC), coupled with effective therapeutic approaches, will improve management of progressive functional impairment in cancer patients. Salidroside, a phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It is widely consumed as a nutritional supplement, but its effects on CAC and the possible mechanism remain a mystery. METHODS: In the murine models of cachexia induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main features of CAC were determined after treatment of salidroside or chemotherapy. In vitro experiments were performed using murine C2C12 myotubes, which were treated by tumour necrosis factor-alpha. Levels of several critical muscle-related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and myosin heavy chain (MyHC) were examined using western blot both in vitro and in vivo. RESULTS: In the present study, we showed the exciting effect of salidroside on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside treatment could effectively preserve the tumour-free body weight, decrease loss of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their survival time. Additionally, in combined chemotherapy, salidroside could synergistically enhance the anti-tumour activity of cisplatin, especially decreased or eliminated chemotherapy-induced cachexia. Further analysis demonstrated that salidroside could significantly increase expression of mTOR, p-mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression in C2C12 myotubes but also effectively rescue their down-regulation induced by tumour necrosis factor-alpha. CONCLUSIONS: In the current study, the exciting effect of salidroside on CAC suggested that salidroside supplementation might be a promising approach for a multi-targeted therapy for the treatment of CAC. FAU - Chen, Xiangzheng AU - Chen X AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Wu, Yangping AU - Wu Y AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Yang, Tinghan AU - Yang T AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Wei, Mingtian AU - Wei M AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Wang, Yuxi AU - Wang Y AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Deng, Xiangbing AU - Deng X AD - Department of Gastrointestinal Surgery, West China Hospital Sichuan University Chengdu Sichuan 610072 China. FAU - Shen, Congcong AU - Shen C AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Li, Wenting AU - Li W AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Zhang, Hang AU - Zhang H AD - Pharmacology & Pharmaceutical Sciences School of Medicine/Collaborative Innovation Center for Biotherapy Tsinghua University Beijing 100084 China. FAU - Xu, Weiyong AU - Xu W AD - Department of Pathology Sichuan Provincial People's Hospital Chengdu Sichuan 610072 China. FAU - Gou, Lantu AU - Gou L AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. FAU - Zeng, Yong AU - Zeng Y AD - Department of Liver Surgery and Liver Transplantation Center, West China Hospital Sichuan University Chengdu Sichuan 610041 China. FAU - Zhang, Yonghui AU - Zhang Y AD - Pharmacology & Pharmaceutical Sciences School of Medicine/Collaborative Innovation Center for Biotherapy Tsinghua University Beijing 100084 China. FAU - Wang, Ziqiang AU - Wang Z AD - Department of Gastrointestinal Surgery, West China Hospital Sichuan University Chengdu Sichuan 610072 China. FAU - Yang, Jinliang AU - Yang J AD - State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School Sichuan University 3-17 Renmin South Road Chengdu Sichuan 610041 China. LA - eng PT - Journal Article DEP - 20160118 PL - Germany TA - J Cachexia Sarcopenia Muscle JT - Journal of cachexia, sarcopenia and muscle JID - 101552883 PMC - PMC4864170 OTO - NOTNLM OT - Cancer-associated cachexia OT - MyHC OT - Salidroside OT - Skeletal muscle OT - mTOR EDAT- 2016/08/06 06:00 MHDA- 2016/08/06 06:01 PMCR- 2016/05/01 CRDT- 2016/08/06 06:00 PHST- 2015/02/25 00:00 [received] PHST- 2015/04/30 00:00 [revised] PHST- 2015/05/04 00:00 [accepted] PHST- 2016/08/06 06:00 [entrez] PHST- 2016/08/06 06:00 [pubmed] PHST- 2016/08/06 06:01 [medline] PHST- 2016/05/01 00:00 [pmc-release] AID - JCSM12054 [pii] AID - 10.1002/jcsm.12054 [doi] PST - ppublish SO - J Cachexia Sarcopenia Muscle. 2016 May;7(2):225-32. doi: 10.1002/jcsm.12054. Epub 2016 Jan 18.