Combinatorial Antitumor Effect of Rapamycin and β-Elemene in Follicular Thyroid Cancer Cells

Biomed Res Int. 2016:2016:6723807. doi: 10.1155/2016/6723807. Epub 2016 May 4.

Abstract

Background. mTOR signaling would be a promising target for thyroid cancer therapy. However, in clinical trials, objective response rate with mTOR inhibitor monotherapy in most cancer types was modest. A new focus on development of combinatorial strategies with rapalogs is increasing. Objective. Investigating the combinatorial antitumor effect of rapamycin and β-elemene in follicular thyroid cancer cells. Methods. MTT assay was used to determine the FTC-133 cell proliferation after culturing with rapamycin and/or β-elemene. To analyze their combinatorial effect, immunoblotting was performed to analyze the activation status of AKT. Moreover, β-elemene attenuated rapamycin-induced immunosuppression was tested in mice. Results. Combination of rapamycin and β-elemene exerted significant synergistic antiproliferative effects in FTC-133 cell lines in vitro, based on inhibiting the AKT feedback activation induced by rapamycin. In vivo, the β-elemene could attenuate rapamycin-induced immunosuppression via reversing imbalance of Treg/Th17, with the underlying mechanism needed to be declared. Conclusions. We demonstrate that the novel combination of mTOR inhibitor with β-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Synergism*
  • Humans
  • Immunosuppression Therapy
  • Mice
  • Sesquiterpenes / administration & dosage*
  • Sirolimus / administration & dosage*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Thyroid Epithelial Cells / drug effects
  • Thyroid Epithelial Cells / immunology
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / immunology
  • Thyroid Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Sesquiterpenes
  • beta-elemene
  • Sirolimus