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Published on: September 6, 2024
Combinatorial Antitumor Effect of Rapamycin and β-Elemene in Follicular Thyroid Cancer Cells
Jun Zhou1, Li-Li He1, Xiao-Fei Ding1
1School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
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.
Insights
Combining rapamycin and β-elemene shows synergistic effects against follicular thyroid cancer cells by inhibiting AKT signaling. This combination also counteracts rapamycin-induced immunosuppression in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- mTOR signaling is a potential therapeutic target for thyroid cancer.
- Monotherapy with mTOR inhibitors has shown modest clinical response rates.
- Combinatorial strategies with rapalogs are gaining traction.
Purpose of the Study:
- To investigate the combined antitumor effects of rapamycin and β-elemene in follicular thyroid cancer (FTC).
- To analyze the impact of this combination on AKT signaling and immune response.
Main Methods:
- MTT assay was used to assess cell proliferation of FTC-133 cells.
- Immunoblotting analyzed AKT activation status.
- In vivo studies in mice evaluated the effect of β-elemene on rapamycin-induced immunosuppression.
Main Results:
- Rapamycin and β-elemene demonstrated synergistic antiproliferative effects on FTC-133 cells in vitro.
- The combination inhibited AKT feedback activation induced by rapamycin.
- In vivo, β-elemene attenuated rapamycin-induced immunosuppression by modulating Treg/Th17 balance.
Conclusions:
- A novel combination of an mTOR inhibitor (rapamycin) and β-elemene synergistically reduces follicular thyroid cancer cell growth.
- This combination impacts key signaling pathways and immune responses.
- Further preclinical validation is warranted for this therapeutic strategy.
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