BI-847325 Induced The Apoptosis And Sodium/Iodide Symporter Expression Of Thyroid Carcinoma Cell Line BCPAP

Objective To investigate the inhibitory effect of BI-847325,a novel MEK inhibitor,on the proliferation of BRAF^V600Emutant thyroid carcinoma cell line BCPAP and the expression regulation of apoptotic proteins as well as sodium/iodide symporter（NIS）.Methods（1）BCPAP cells were treated for 48 h with different concentrations of BI-847325.The effect of BI-847325 on the proliferation of BCPAP cells was investigated by the CCK-8 assay;the apoptosis of BCPAP cells was evaluated by the flow cytometry;the activation level of MEK and its downstream apoptotic and iodine-uptake proteins NIS were analyzed by Western Blotting.（2）5μM vemurafenib treated BCPAP cells for 2weeks to establishe vemurafenib-resistant BCPAP cell lines,treated for 48 h with different concentrations of BI-847325,the effect of BI-847325 on the proliferation of vemurafenib-resistant BCPAP cells was investigated by the CCK-8 assay,and the activation level of MEK was analyzed by Western Blotting.Results（1）BI-847325 inhibited the proliferation of BCPAP cells and the IC50 of BI-847325 for 48h was 0.46μM.（2）BI-847325 induced apoptosis of BCPAP cells,and the apoptosis rate was（26.41±2.23）%when the concentration was 0.4μM.（3）BI-847325decreased the activation level of MEK 1/2、ERK 1/2,and adjusted the expression of BIM,BAX and BCL-2.（4）BI-847325 up-regulated the expression of sodium/iodide symporter（NIS）.（5）BI-847325 inhibited the proliferation of vemurafenib-resistant BCPAP cell lines and the IC₅₀of BI-847325 for 48 h was 0.55μM.Conclusion BI-847325 induced the apoptosis of BCPAP and vemurafenib-resistant BCPAP cells by inhibiting the activation level of MEK/ERK;BI-847325 up-regulated the expression of NIS,which might increase the ¹³¹I uptake of BCPAP cells.