| Purpose To study the effects of new synthetized 12 kinds of all-trans retinoic acid(ATRA)derivatives on human pulmonary adenocarcinoma cell line A549 in vitro and its mechanisms.Methods The A549 cells were respectively treated by ATRA and ATRA derivatives at the dose of (1,5,10)μg/ml for 1,2,3,7 days.The morphologic change of A549 was observed by light microscope,and the diversity of CEA was detected by CEA kit.The proliferation of A549 cells was observed by MTT assay,and the cell cycle and apoptosis were detected by flow cytometry. The related protein expression was analyzed by Western blot.Results The A549 cells were respectively treated by ATRA and 12 kinds of ATRA derivatives at the dose of (1,5,10)μg/ml for 3 days,which showed varying degrees of proliferation inhibition. 6 kinds of the ATRA derivatives displayed high proliferation inhibition on A549 cells.Proliferation inhibition rate increased with the drug concentration increasing,13.5%,15.4%,29.1%(YXY070817,DMSO),18.7%,27.3%,30.5%(SHI060925,DMSO),12.3%,13.6%,27.0%(YXY070822,DMSO),9.1%,17.8%,47.0%(YXY070710,DMSO),12.2%,16.7%,26.0%(YXY070702,Ethanol),11.9%,13.3%,45.0%(YXY070911,DMSO)respectively.The highest inhibition rate is 47.0%(P<0.05).The A549 cells were respectively treated by ATRA and above 6 kinds of ATRA derivatives at the dose of 10μg/ml for 1,2,3,7 days,Proliferation inhibition rate increased with the action time increasing,9.5%,13.0%,33.4%,75.9%(YXY070817,DMSO),23.3%,26.1%,35.5%,40.2%(SHI060925,DMSO),10.8%,14.0%,27.1%,37.2%(YXY070822,DMSO),18.1%,20.6%, 40.4%,83.4%(YXY070710,DMSO),6.6%,18.2%,23.8%,25.4%(YXY070702,Ethanol),7.6%,16.2%,32.2%,41.3%(YXY070911,DMSO)respectively.The highest inhibition rate is 83.4%(P<0.05).The A549 cells were respectively treated by ATRA and these 6 kinds of ATRA derivatives at the dose of 10μg/ml for 3 days,the A549 cells morphology changed evidently.The cells turn from fusiform into round,with the cells swelling , cytoplasm raritas , permeability increasing , plasmalemma fragmentation.The A549 cells were respectively treated by ATRA and 6 kinds of ATRA derivatives at the dose of 10μg/ml for 3 days,the secretary amount of CEA decreased evidently compared with control group,(3.27±0.21)μg/L(YXY070817,DMSO),(3.20±0.26)μg/L(SHI060925,DMSO),(2.93±0.15)μg/L(YXY070710,DMSO),(3.13±0.25)μg/L(YXY070822,DMSO),(4.03±0.15)μg/L(YXY070702,Ethanol),(3.37±0.31)μg/L(YXY070911,DMSO)respectively(P<0.05).The A549 cells were respectively treated by ATRA and 6 kinds of ATRA derivatives at the dose of 10μg/ml for 3 days,in G0-G1 phase these cells were obviously decreased,also the apoptosis appeared.In 10μg/ml YXY070710 group,the apoptosis rate is 47.0%(P<0.05),apoptosis peak moved in advance.The A549 cells were respectively treated by ATRA and ATRA derivate(YXY070710,DMSO)at the dose of(1,10)μg/ml for 3 days,the expression of Bcl-2 protein decreased evidently in 10μg/mlYXY070710 group without marked change in 1μg/mlYXY070710 group.There have no marked change of Bax,Bak,Caspase-3 proenzyme,p53,NF-κB expression in two concentration of ATRA and YXY070710 group.Conclusion 12 kinds of ATRA derivatives have variedly proliferation inhibition effect on A549 cells,6 kinds of which have a stronger contribution to A549 cells proliferation inhibition,and can lead to cell morphological changes,reduce the secretory volume of CEA,variedly induce cell apoptosis. ATRA derivatives may induce tumour cell apopotosis through decreasing Bc1-2 expression, which may be one of the mechanism on their anticancer.
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