A Novel All-trans Retinoid Acid Derivatives Inhibits The Migration Of Breast Cancer Cell Lines MDA-MB-231via Myosin Light Chain Kinase Involving P38-MAPK

Objective To explore the effect and its probable mechanism of a synthetic retinoid4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) on the migration ability of humanbreast cancer MDA-MB-231CellsMethods MTT assay was performed to measure the proliferation of MDA-MB-231cells treated with different concentrations of ATPR. The effect of ATPR and ML-7,aselective inhibitor of MLCK and SB203580, a inhibit of p38,on the migration ofMDA-MB-231Cells was analyzed by wound healing assay.The expression of myosinlight chain kinase (MLCK)and phosphorylation of myosin light chain (MLC) of theMDA-MB-231Cell in48h were detected by western bolt. Phosphorylation of ERK,JNK, p38in2h and48h were detected by western blot. At the same time,Phosphorylation of p38in the MDA-MB-231Cell that was treated by ML-7, in2hwas measured and MLCK and p-MLC were detected.Results The OD value of ATRA group decreased from0.439±0.014,0.446±0.025,0.389±0.028,0.146±0.018,0.104±0.013,0.116±0.006to0.115±0.006while the OD value of ATPR group decreased from0.474±0.025,0.128±0.009,0.115±0.005,0.109±0.011,0.124±0.004,0.113±0.007to0.133±0.010at different concentration(10,20,30,40,50,60,70μmol/l). According to the above data, IC50of ATRA is34.08μmol/l and ATPR is18.06μmol/l. The relative migration rate of ATPR groupreached50%at48h while the relative migration rate of ATRA group reached over90%.The relative migration rate of ML-7group and SB group had significant decreasecompared with control group. The expression level of MLCK and phosphorylation ofMLC of breast cancer cells reduced when the cells were treated by ATPR with48h,the phosphorylation of ERK, JNK and p38in breast cancer also reduced when cellswere treated by ATPR with2h. in addition, ML-7(50μmol/l) could inhibit thephosphorylation of p38and SB (50μmol/l) could inhibit the expression of MLCK andphosphorylation of MLC.Conclusions ATPR had a better inhibition on the proliferation and the migration ofbreast cancer MDA-MB-231cells than ATRA and its probable mechanism wasassociated with the down regulation of expression of MLCK and phosphorylation ofMLC protein involving p38-MAPK pathway.