Huaier aqueous extract sensitizes cells to rapamycin and cisplatin through activating mTOR signaling

J Ethnopharmacol. 2016 Jun 20;186:143-150. doi: 10.1016/j.jep.2016.03.069. Epub 2016 Apr 1.

Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and 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.

Keywords: Cancer; Cisplatin; Huaier; Rapamycin; mTOR.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Mice
  • Rats
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • TOR Serine-Threonine Kinases
  • Cisplatin
  • Sirolimus