Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid malignancy, with an increasing incidence worldwide. Although conventional treatments are effective for many patients, some individuals encounter resistance or lack appropriate therapeutic options. This highlights the necessity for alternative therapeutic strategies. Drug repositioning has emerged as a promising approach in oncology, providing a faster and cost-effective manner for new treatments. This study aimed to identify potential repositioned drug candidates for PTC treatment and conduct their preliminary in vitro evaluation using a PTC cell line.

Four microarray datasets (GSE6339, GSE3467, GSE27155, and GSE138198) were analyzed to identify differentially expressed genes (DEGs) between normal and PTC tissues. Drug repositioning was conducted based on commonly upregulated and downregulated genes using L1000CDS² search engine. The gene expression signatures method was employed to identify potential therapeutic molecules, leading to the identification of 50 repositioned drug candidates. Selected candidates were tested on the MDA-T32 PTC cell line to evaluate IC50 values.

The IC50 values of the tested drugs varied considerably against MDA-T32 cells. NSC632839 exhibited the highest cytotoxicity, with an IC50 value of 178.9 nM, followed by MP7 (2.166 µM), Iodophenpropit dihydrobromide (7.325 µM), and H89 (10.85 µM), indicating their strong inhibitory effects on MDA-T32 cell viability. Other tested compounds, including Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (14.59 µM), L741,626 (18.05 µM), and L732,138 (68.56 µM), demonstrated moderate cytotoxicity, whereas Clofibric acid showed the lowest potency (3.926 mM) against PTC.

These findings indicate that NSC632839 and MP7 may serve as promising candidates for further evaluations. Future studies should focus on elucidating mechanisms of action and validating the therapeutic potential of those repositioned drugs.