A novel all-trans retinoid acid derivatives inhibits the migration of breast cancer cell lines MDA-MB-231 via myosin light chain kinase involving p38-MAPK pathway
A novel all-trans retinoid acid derivatives inhibits the migration of breast cancer cell lines MDA-MB-231 via myosin light chain kinase involving p38-MAPK pathway
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一种新型全反式维A酸衍生物通过涉及p38-MAPK通路的肌球蛋白轻链激酶抑制乳腺癌细胞系MDA-MB-231的迁移
DOI：
10.1016/j.biopha.2013.03.016
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发表时间：
2013-06-01
影响因子：
7.5
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
--
作者：
Wang, Bei;Yan, Yunwen;Wang, Yuan
目的：目的：探讨合成维甲酸4-氨基-2-三氟甲基苯酯（ATPR）对人乳腺癌MDA-MB-231细胞迁移的影响及其可能机制。采用创伤愈合实验检测ATPR、肌球蛋白轻链激酶（MLCK）选择性抑制剂ML-7和p38抑制剂SB 203580对MDA-MB-231细胞迁移的影响。Western blot检测MLCK的表达及肌球蛋白轻链（MLC）、ERK、JNK、p38蛋白的磷酸化。结果：ATRA和ATPR处理后，MDA-MB-231细胞的增殖和迁移能力明显受到抑制。ATRA和ATPR的IC 50分别为34.08 μ mol/l和18.06 μ mol/l。ATPR组MDA-MB-231细胞48 h相对迁移率达50%，ATRA组达90%以上。ML-7组和SB组的相对迁移率较对照组明显降低。ATPR处理48 h后，乳腺癌细胞MLCK的表达水平和MLC的磷酸化水平降低，ATPR处理2 h后，乳腺癌细胞ERK、JNK和p38的磷酸化水平也降低。此外，ML-7 50 μ mol/l的H2 O2能抑制p38和SB的磷酸化50 μ mol/L的H2 O2能抑制MLCK的表达和MLC的磷酸化。ATPR对乳腺癌MD-AMB-231细胞增殖和迁移的抑制作用优于ATRA，其机制可能与p38-MAPK通路参与MLCK表达下调和MLC蛋白磷酸化有关。(C)2013年Elsevier Masson SAS。All rights reserved.
Objective: To explore the effect and its probable mechanism of a synthetic retinoid 4-amino-2-trifluoromethyl-phenyl ester (ATPR) on the migration of human breast cancer MDA-MB-231 cells.Methods: MTT assay was performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. The effect of ATPR and ML-7, a selective inhibitor of myosin light chain kinase (MLCK), and SB203580, an inhibitor of p38, on the migration of MDA-MB-231 cells were analyzed by wound healing assay. The expression of MLCK and phosphorylation of myosin light chain (MLC), ERK, JNK, p38 proteins were detected by western blotResults: After the cells were treated by ATRA and ATPR, the proliferation and migration of breast cancer MDA-MB-231 cells were inhibited significantly. The IC 50 of ATRA and ATPR is 34.08 mu mol/l and 18.06 mu mol/l respectively. The relative migration rate of MDA-MB-231 cells treated with ATPR reached 50% at 48 h while the ATRA group is over 90%. The relative migration rate of ML-7 group and SB group had significant decrease compared with control group. The expression level of MLCK and phosphorylation of MLC of breast cancer cells was reduced when the cells were treated by ATPR with 48 h, the phosphorylation of ERK, JNK and p38 in breast cancer also reduced when cells were treated by ATPR with 2 h. In addition, ML-7 (50 mu mol/l) could inhibit the phosphorylation of p38 and SB (50 mu mol/l) could inhibit the expression of MLCK and phosphorylation of MLC.Conclusions: ATPR had a better inhibition on the proliferation and the migration of breast cancer MD-AMB-231 cells than ATRA, and its probable mechanism was associated with the down regulation of expression of MLCK and phosphorylation of MLC protein involving p38-MAPK pathway. (C) 2013 Elsevier Masson SAS. All rights reserved.