New Insights into 4-Amino-2-tri-fluoromethyl-phenyl Ester Inhibition of Cell Growth and Migration in the A549 Lung Adenocarcinoma Cell Line

Objective: The present study was designed to investigate the probable mechanisms of synthetic retinoid4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 humanlung carcinoma cells. Materials and
Methods: After the A549 cells were treated with different concentrationsof ATPR or all-trans retinoic acid (ATRA) for 72 h, scratch-wound assays were performed to assess migration.Immunofluorescence was used to determine the distribution of CAV1 and RXRα, while expression of CAV1,MLCK, MLC, P38, and phosphorylation of MLC and P38 were detected by Western blotting.
Results: ATPRcould block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreasedcompared with control group. In addition, ATPR decreased the expression of a migration related proteins,MLCK, and phosphorylation of MLC and P38. ATPR could also influence the expression of RARs or RXRs. Atthe same time, CAV1 accumulated at cell membranes, and RXRα relocated to the nucleus after ATPR treatment.
Conclusions: Caveolae may be implicate in the transport of ATPR to the nucleus. Change in the expression anddistribution of RXRα may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPRreduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC andP38.