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Radiosensitization Following Valproic Acid and Gamma Rays in Anaplastic Thyroid Cancer Cells Increases the Expression
Marina Perona1, Cecilia Grissi2, Cinthia Rosemblit3
1Department of Radiobiology, National Atomic Energy Commission, San Martín, Buenos Aires, Argentina; National Scientific and Technical Research Council, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Archives of Medical Research
|May 1, 2025
Summary
Valproic acid (VA) combined with gamma radiation alters microRNA (miR) expression in anaplastic thyroid cancer (ATC) cells. This novel miR profile may enhance radiosensitivity in treating this lethal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis, necessitating improved treatment strategies.
- Radiotherapy is a key component of ATC treatment, and its efficacy can be enhanced by radiosensitizing agents.
- Valproic acid (VA), a histone deacetylase inhibitor, has demonstrated radiosensitizing properties in various cancer types, including thyroid cancer.
Purpose of the Study:
- To investigate the effect of combined valproic acid (VA) and gamma radiation on microRNA (miR) expression in radioresistant anaplastic thyroid cancer (ATC) cells.
- To identify specific miRs that are differentially expressed following combined treatment and may contribute to radiosensitization.
Main Methods:
- Anaplastic thyroid cancer cell lines (8505c and KTC-2) were treated with VA and exposed to 2 Gy gamma radiation.
- Microarray analysis was performed on 8505c cells to assess miR expression profiles 4 hours post-irradiation.
- Quantitative real-time PCR (RT-qPCR) was used to validate the expression of selected miRs in both cell lines.
Main Results:
- Combined VA and gamma irradiation resulted in 109 differentially expressed miRs in 8505c cells compared to irradiation alone.
- Upregulation of hsa-miR-26a-5p, a miR typically downregulated in aggressive thyroid cancers, was observed, suggesting a radiosensitization effect.
- Downregulation of hsa-miR-27a-3p and hsa-miR-486-5p was noted after irradiation and VA treatment, respectively. These findings were validated in both ATC cell lines.
Conclusions:
- The study identified a novel microRNA expression profile regulated by the combination of VA and gamma irradiation in ATC cells.
- These findings suggest a potential role for these regulated miRs in mediating radio-induced response and radiosensitization in anaplastic thyroid cancer.
- Further research into this miR expression profile could lead to new therapeutic strategies for ATC.
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