Effect Of All-trans Retinoic Acid And Its Derivative4-amino-2-trifluoromethyl-phenyl Ester On Proliferation, Migration Ability, And Expression Of Osteopontin In Human Pulmonary Adenocarcinoma A549Cells And Their Mechanism

Objective To investigate the effect of all-trans retinoic acid(ATRA) and its derivative4-amino-2-trifluoromethyl-phenyl ester(ATPR) on the proliferation inhibition, migrationability,and expression of osteopontin of A549cells and and their mechanism.Methods A549cells were treated with ATRA and ATPR in different concentration (1、2.5、5、7.5、10、25、50mg/L) for3days, and with5mg/L ATRA or ATPR for1,3,7days,respectively. Then the proliferation of A549cells was detected by MTT assay. Themigration ability of A549cells was measured by scarification test. The expression ofOPN, JNKand p-JNK in A549cells was observed by Western blot. The possible signaltransduct pathway was analyzed by addition of JNK inhibitor (SP600125) in A549cellstreated with ATRA or ATPA in different concentration. Statistical analysis wasperformed by using SPSS13.0. Experimental data were represented with Mean±SD.Comparison correlated data was used by Spearman method. P<0.05was considered assignificant difference.Results ATRA and ATPR could inhibit the proliferation of A549cells in adose-dependent and time-dependent manner. The IC50of ATRA and ATPR were11.5mg/L and4.6mg/L, respectively, which showed the inhibition effect of ATPA onA549cells proliferation was more obviously than that of ATRA. The scarification test showed that ATRA and ATPR could inhibit A549cells’ migration, the distance ofmigration was decreased with the increasing of drug concentration, The results ofWestern blot indicated that ATRA and ATPR could inhibit the expression of OPN andup-regulate the phosphorylation of JNK, but had no effect on the expression JNK. AfterA549cells was treated with ATRA or ATPR and SP600125, the result showedantagonism effect of inhibiting cells proliferation, migration and the down regulation ofthe expression of OPN, compared with A549cells treaed only ATRA or ATPR（P<0.05）,while SP600125had no above effection. A positive correlation was found between thecell proliferation and the expression of OPN in A549cells（r=0.971, P=0.01）.Conclusion ATRA and ATPR could inhibit the proliferation, migration of A549cells, aswell as expression of OPN, and appeared obviously positive correlation between them.Inhibiting the expression of OPN in tumor cells by activating JNK pathway may be oneof the anti-tumor mechanisms of ATRA and its derivatives.