Combinatorial Antitumor Effect of Rapamycin and β-Elemene in Follicular Thyroid Cancer Cells.
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.
School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
Jun
J
Zhou
School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
Li-Li
LL
He
School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
Xiao-Fei
XF
Ding
Taizhou Enze Hospital, Taizhou, Zhejiang 318000, China.
Qiu-Qi
QQ
Yuan
School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
Jian-Xin
JX
Zhang
Taizhou Municipal Hospital, Taizhou, Zhejiang 318000, China.
Shuang-Chun
SC
Liu
School of Pharmaceutical and Chemical Engineering, Taizhou University, Taizhou, Zhejiang 318000, China; Institute of Tumor, Taizhou University, Taizhou, Zhejiang 318000, China.
Guang
G
Chen
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007165:Immunosuppression Therapy; D051379:Mice; D012717:Sesquiterpenes / Q000008:administration & dosage*; D020123:Sirolimus / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D000072637:Thyroid Epithelial Cells / Q000187:drug effects / Q000276:immunology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D012717:Sesquiterpenes; C445979:beta-elemene; D020123:Sirolimus