Background and purpose: Redifferentiation therapy with MAPK inhibitor is a novel strategy for radioiodine-refractory differentiated thyroid cancer

but its efficacy is relatively low. Histone deacetylase inhibitor (HDACI) is another kind of redifferetiation drug

given histone deacetylation at the sodium/iodide symporter (NIS) promoter by histone deacetylase (HDAC) as a mechanism

combined therapy using HDACI and BRAF/MEK inhibitor may produce better effect. In the present study

we assessed whether combining HDACI with BRAF/MEK inhibitor suppressing both BRAF/MEK and HDAC could mor

e effectively induce thyroid gene expression and radioiodine uptake in thyroid cancer cells. Methods: We tested iodine and glucose handling gene expression and radioiodine uptake in BCPAP

K1

BHP 2-7 cells treated with dabrafenib/selumetinib and panobinostat alone or in combination using (real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR)

Western blot

immunofluorescence

flow cytometry

radionuclide uptake/efflux assay and in vitro clonogenic assay. Results: Dabrafenib/selumetinib induced modest expression of thyroid genes and radioiodine uptake and suppressed GLUT1 expression in BCPAP and K1 cells

panobinostat showed redifferetiation effect in all the cells. Dabrafenib/selumetinib and panobinostat showed synergistic effect on redifferentiation in BCPAP and K1 cells. Conclusion: Simultaneously suppressing BRAF/MEK and HDAC induced more robust expression of thyroid genes and radioiodine uptake in thyroid cancer cells harboring BRAF

V600E

compared with suppressing BRAF/MEK or HDAC alone

which warrants further investigation in animal and clinical trials.