Inhibitory effect of vemurafenib combined with panobinostat on human anaplastic thyroid cancer cells.

[BACKGROUND] Anaplastic thyroid cancer (ATC) is a highly malignant tumor with poor prognosis and limited therapeutic options, creating an urgent need for novel treatments.

[OBJECTIVES] This study aimed to investigate the inhibitory effect of Vemurafenib (Ve) combined with Panobinostat (Pa) on human ATC cells (FRO and ARO) and its underlying mechanism.

[METHODS] Four groups were established: Control, Ve, Pa, and Ve+Pa. Cell proliferation and drug synergy were analyzed using CCK-8 assay, colony formation assay, and CompuSyn software. Cell migration, invasion, apoptosis, and glucose consumption were detected by Transwell assay, wound healing assay, apoptosis assay, and glucose consumption assay, respectively. Molecular markers were examined via RT-qPCR, Western blotting, and immunofluorescence.

[RESULTS] CompuSyn analysis verified the synergistic effect of Ve+Pa in FRO and ARO cells. Compared with the other three groups, the Ve+Pa group showed significantly suppressed cell proliferation, migration, invasion, and glucose consumption, as well as enhanced apoptosis. Moreover, the mRNA and protein expression of the sodium iodide symporter (NIS) and iodine metabolism-related molecules was upregulated, whereas glucose transporter 1 (GLUT1) expression was downregulated.

[CONCLUSION] Ve combined with Pa exerts a synergistic inhibitory effect on the growth and metastasis of FRO and ARO cells, while promoting apoptosis and cellular redifferentiation. This combination may provide a potential therapeutic strategy for ATC.