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 retinoid 4-amino-2-tri-fluoromethyl-phenyl ester (ATPR) inhibition of the proliferation and migration of A549 human lung carcinoma cells.


METHODS
After the A549 cells were treated with different concentrations of 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
ATPR could block the migration of A549 cells. The relative migration rate of ML-7 group had significantly decreased compared 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. At the 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 and distribution of RXRα may be implicated in ATPR inhibition of A549 cell proliferation. The mechanisms of ATPR reduction in A549 cell migration may be associated with expression of MLCK and phosphorylation of MLC and P38.
Department of Respiratory Medicine, the First Affiliated Hospital, Hefei, Anhui, China E-mail : guishuyu@126.com, wangyuan@ahmu.edu.cn.
Hao
H
Wang
Shu-Yu
SY
Gui
Fei-Hu
FH
Chen
Qing
Q
Zhou
Yuan
Y
Wang
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001381:Azepines / Q000494:pharmacology; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D047488:Retinoid X Receptors / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000187:drug effects*
C585745:4-amino-2-trifluoromethyl-phenyl retinate; D000970:Antineoplastic Agents; D001381:Azepines; C495540:CAV1 protein, human; D051242:Caveolin 1; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D047488:Retinoid X Receptors; D012176:Retinoids; C070571:ML 7; D014212:Tretinoin; D009219:Myosin-Light-Chain Kinase