Validation of EZH2 Inhibitor Efficiency in Anaplastic Thyroid Carcinoma Cell Lines
Hirotaka Nakayama1,2, Nao Saito3,4, Rika Kasajima5
1Department of Surgery, Hiratsuka Kyosai Hospital, Hiratsuka, Japan.
Background/Aim:
The prognosis of anaplastic thyroid carcinoma (ATC) is poor, and there is currently no established treatment to improve its outcome. We previously reported that enhancer of zeste homolog 2 (EZH2) was highly expressed in ATC, and may be a therapeutic target; however, the effects of EZH2 on ATC growth currently remain unknown.
Materials And Methods:
We investigated the effects of an EZH2 inhibitor (DZNep) on four ATC cell lines (8305C, KTA1, TTA1 and TTA2). We performed a gene panel analysis of all ATC cell lines to identify differences in DZNep sensitivity between the cell lines. To investigate the effects of DZNep on the recovery of differentiation, we assessed changes in thyroid differentiation markers (TDMs) before and after the DZNep treatment using PCR.
Results:
EZH2 was expressed in all ATC cell lines. The cell-reducing effects of DZNep were detected in all ATC cell lines, and were the strongest in KTA1 cells followed by TTA2 cells. The TTA1 and 8305C cell lines, which showed weak cell-reducing effects, had TP53 mutations. No changes in TDMs were observed in any ATC cell line.
Conclusion:
DZNep, an EZH2 inhibitor, exerted suppressive effects on the growth of ATC cell lines and has potential as a therapeutic strategy; however, its effects may be attenuated in ATC with TP53 mutations.
Insights
An enhancer of zeste homolog 2 (EZH2) inhibitor, DZNep, suppressed anaplastic thyroid carcinoma (ATC) cell growth. However, TP53 mutations may reduce DZNep
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Anaplastic thyroid carcinoma (ATC) has a poor prognosis with limited treatment options.
- Enhancer of zeste homolog 2 (EZH2) is highly expressed in ATC and is a potential therapeutic target.
- The specific effects of EZH2 inhibition on ATC growth were previously unknown.
Purpose of the Study:
- To investigate the effects of the EZH2 inhibitor DZNep on anaplastic thyroid carcinoma (ATC) cell lines.
- To identify factors influencing DZNep sensitivity in ATC.
- To assess DZNep's impact on thyroid differentiation markers.
Main Methods:
- Treatment of four ATC cell lines (8305C, KTA1, TTA1, TTA2) with DZNep.
- Gene panel analysis to determine DZNep sensitivity.
- Polymerase chain reaction (PCR) to evaluate thyroid differentiation markers (TDMs) before and after DZNep treatment.
Main Results:
- EZH2 expression was confirmed in all tested ATC cell lines.
- DZNep demonstrated cell-reducing effects across all cell lines, with the strongest impact on KTA1 and TTA2.
- TP53 mutations were associated with weaker DZNep efficacy in TTA1 and 8305C cell lines; no changes in TDMs were observed.
Conclusions:
- DZNep exhibits suppressive effects on ATC cell growth, indicating its potential as a therapeutic strategy.
- The efficacy of DZNep in ATC may be diminished in tumors with TP53 mutations.
- Further research is warranted to explore EZH2 inhibition in ATC treatment.
