N-(3-三氟甲基苯基)维甲酰胺对人肺腺癌A549细胞分化和骨桥蛋白表达的影响

摘要

Objective To investigate the effects of ATRA derivant N-(3-trifluoromethyl-phenyl)-retinamide (NTFMP) on the differentiaton and expression of osteopontin(OPN) of human pulmonary adenocarcinoma A549 cells.Methods A549 cells were treated with ATRA and NTFMP, respectively. The proliferation of A549 cells was observed by MTT assay. The morphology of A549 was observed by light microscope and the diversity of carcinoembryonic antigen(CEA) was detected by kinetics analysis cytometry. The related protein expression was analyzed by Western blot. Results The NTFMP could inhibit the proliferation of A549 cells in a dose-dependent manner. The carcinoembryonic antigen(CEA) level decreased evidently in NTFMP group at 10 mg/L. Compared with control group, A549 cells in NTFMP group became lesser, more irregular, non-overlapping and monolayer. The results of Western blot indicated that the expression of phosphorylation of ERK1/2 and OPN were down-regulated significantly in A549 cells treated with NTFMP at 7.5 mg/L. Conclusion NTFMP can inhibit the A549 cells proliferation and induce differentiation, the mechanism of which possibly is to inhibit the phosphorylation of ERK1/2 and decrease the expression of OPN.%目的 分析新合成的全反式维甲酸(ATRA)衍生物N-(3-三氟甲基苯基)维甲酰胺(NTFMP)对人肺腺癌细胞株A549体外增殖、分化及骨桥蛋白表达的影响.方法 以人肺腺癌细胞株A549为研究对象,分别给予不同浓度的ATRA及NTFMP进行干预,应用四甲基偶氮唑蓝比色(MTT)法测定A549细胞的增殖情况;酶动力学法检测该药对A549细胞分泌癌胚抗原(CEA)的影响;光学显微镜观察A549细胞形态变化;Western blot检测细胞外调节蛋白激酶(ERK1/2)蛋白及骨桥蛋白(OPN)表达的变化.结果 NTFMP处理组A549细胞增殖抑制率随药物浓度的增加而增高;10 mg/L的NTFMP可明显抑制CEA的分泌;与对照组比较,细胞数量明显减少,形态由梭形变为不规则形,不重叠,呈单层生长;Western blot检测显示磷酰化的细胞外调节蛋白激酶(pERK1/2)及OPN在A549细胞内均呈高表达,7.5 mg/L NTFMP显著抑制ERK1/2磷酸化和OPN的表达.结论 NTFMP对A549细胞具有促进分化、抑制增殖作用;其机制可能与下调A549细胞ERK1/2磷酸化水平及抑制OPN的表达相关.