title: Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via activating mTOR signalling.
abstract: 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-α. 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-α.
  
  
  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.
authors: 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.
authors: Xiangzheng
authors: X
authors: Chen
authors: 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.
authors: Yangping
authors: Y
authors: Wu
authors: 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.
authors: Tinghan
authors: T
authors: Yang
authors: 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.
authors: Mingtian
authors: M
authors: Wei
authors: 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.
authors: Yuxi
authors: Y
authors: Wang
authors: Department of Gastrointestinal Surgery, West China Hospital Sichuan University Chengdu Sichuan 610072 China.
authors: Xiangbing
authors: X
authors: Deng
authors: 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.
authors: Congcong
authors: C
authors: Shen
authors: 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.
authors: Wenting
authors: W
authors: Li
authors: Pharmacology & Pharmaceutical Sciences School of Medicine/Collaborative Innovation Center for Biotherapy Tsinghua University Beijing 100084 China.
authors: Hang
authors: H
authors: Zhang
authors: Department of Pathology Sichuan Provincial People's Hospital Chengdu Sichuan 610072 China.
authors: Weiyong
authors: W
authors: Xu
authors: 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.
authors: Lantu
authors: L
authors: Gou
authors: Department of Liver Surgery and Liver Transplantation Center, West China Hospital Sichuan University Chengdu Sichuan 610041 China.
authors: Yong
authors: Y
authors: Zeng
authors: Pharmacology & Pharmaceutical Sciences School of Medicine/Collaborative Innovation Center for Biotherapy Tsinghua University Beijing 100084 China.
authors: Yonghui
authors: Y
authors: Zhang
authors: Department of Gastrointestinal Surgery, West China Hospital Sichuan University Chengdu Sichuan 610072 China.
authors: Ziqiang
authors: Z
authors: Wang
authors: 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.
authors: Jinliang
authors: J
authors: Yang
keywords: Cancer‐associated cachexia; MyHC; Salidroside; Skeletal muscle; mTOR