title: Huaier aqueous extract sensitizes cells to rapamycin and cisplatin through activating mTOR signaling.
abstract: BACKGROUND
  Traditional Chinese Medicine (TCM) has been increasingly used to treat cancers. Trametes robiniophila Murr. (Huaier) is a medicinal fungus for treatment of inflammation and cancer. Huaier Granule has great clinical effect in various types of cancers, including liver cancer, lung cancer, gastric cancer, and breast cancer.
  
  
  OBJECTIVE
  The present study was performed to determine the therapeutical effect of Huaier on cancers caused by aberrant mTOR signaling in vitro and in vivo, investigate the combination effect of Huaier and rapamycin or cisplatin on cell viability, and explore its underlying mechanism.
  
  
  METHODS
  The therapeutical effect of Huaier on cancers caused by aberrant mTOR signaling and the underlying mechanism of combination effect of Huaier and rapamycin or cisplatin on cell viability were investigated in mouse embryonic fibroblasts, rat uterine leiomyoma cells, human hepatoma cells, human lung carcinoma cells, and xenograft tumor model by cell viability assay and immunoblotting.
  
  
  RESULTS
  Activation of mTOR sensitizes cells to Huaier treatment. Huaier inhibits tumorigenic capacity of cells with activated mTOR in vivo. Moreover, activation of mTOR signaling induced by Huaier contributes to the increased sensitivity of cells to rapamycin or cisplatin in response to Huaier treatment.
  
  
  CONCLUSIONS
  Huaier may be a potential drug for the treatment of cancers caused by aberrant mTOR signaling. The combination of Huaier and rapamycin may be a candidate regimen in the treatment of these cancers.
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Zhongdong
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
authors.forename: Ailin
authors.initials: A
authors.lastname: Yang
authors.affiliation: College of Bioengineering, Beijing Polytechnic, Beijing 100029, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Molecular Orthopaedics, Beijing Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei 230032, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zha
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: pengfeitu@163.com.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D051381:Rats; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin; D020123:Sirolimus
keywords: Cancer; Cisplatin; Huaier; Rapamycin; mTOR