三氧化二砷联合非诺贝特对人肺癌A549细胞上皮间质转化及E-cadherin/Snail转化因子的影响  

Effect of combined arsenic trioxide and fenofibrate on epithelial-interstitial transformation and E-cadherin/Snail transformation factor in human pulmonary carcinoma A549 cells

作　　者：王绩英[1] 王涛[1] 曾锦荣[1] 刘春妮[1] 莫碧文[1] 陈梅唏[1] 陈峰[1] 林武洲[1] 

机构地区：[1]桂林医学院附属医院呼吸内科,广西桂林541001

出　　处：《第三军医大学学报》2012年第14期1406-1410,共5页Journal of Third Military Medical University

基　　金：广西壮族自治区卫生厅重点科研课题(重2010046)~~

摘　　要：目的观察三氧化二砷和非诺贝特单独及联合运用对人肺癌A549细胞上皮间质转化及相关因子E-cad-herin、Snail的影响。方法体外培养人肺癌A549细胞,根据处理因素不同分为4组,A组:阴性对照组(只含有DMEM培养液);B组:1μmol/L三氧化二砷单药处理组;C组:100μmol/L非诺贝特单药处理组;D组:1μmol/L三氧化二砷+100μmol/L非诺贝特联合处理组。干预A549细胞48 h后,分别运用MTT法检测对A549细胞的抑制作用,流式细胞术检测对A549细胞周期的影响,小室侵袭实验检测对A549细胞侵袭能力的影响,半定量RT-PCR检测对E-cadherin、SnailmRNA表达的影响,Western blot检测对E-cadherin、Snail蛋白表达的影响。结果与阴性对照组及单药组相比,三氧化二砷联合非诺贝特可以明显抑制A549细胞的活性,其中三氧化二砷组的抑制率为(17.62±0.51)%,非诺贝特组的抑制率为(28.30±0.27)%,而联合组的抑制率为(35.19±0.04)%,差异有统计学意义(P<0.05)。两者联合还可以干扰A549细胞的细胞周期,减弱A549细胞的侵袭能力,3组的侵袭抑制率分别为:三氧化二砷组(50.3±0.15)%,非诺贝特组(56.7±0.57)%,联合组(68.1±0.21)%,差异有统计学意义(P<0.05)。RT-PCR和Western blot检测结果显示,联合组较阴性组及单药组明显上调E-cadherin mRNA及蛋白的表达,下调Snail mRNA及蛋白的表达,差异有统计学意义(P<0.05)。结论三氧化二砷联合非诺贝特有明显的增效作用,两者联合可以增加影响人肺癌A549细胞的上皮间质转化的效果,其机制可能与E-cadherin及Snail相关。Objective To observe the effect of combined arsenic trioxide and fenofibrate on epithelial- interstitial transformation and E-eadherin/Snail transformation factor in human pulmonary carcinoma A549 cells. Methods Human pulmonary carcinoma A549 cells, cultured in vitro,were divided into group A （control group） containing only DMEM culture fluid, group B （ 1 μmol/L arsenic trioxide treatment group）, group C （ 100 μmol/L fenofibrate treatment group）, and group D （ 1 μmol/L arsenic trioxide plus 100 μmol/L fenofi- brate treatment group）. After the A549 ceils were exposed to arsenic trioxide, fenofibrate, arsenic trioxide, and fenofibrate, respectively, for 48 h in vitro, their inhibitory effect on proliferation, cell cycle, invasive ability of A549 cells, and expression of E-cadherin/Snail mRNA and protein in A549 ceils were detected by MTT assay, flow cytometry, RT-PCR and Western blotting, respectively. Results The activity of A549 cells was signifi- cantly lower in group D than in groups A to C. The inhibition rate of the activity of A549 cells was （ 17.62 ± 0.51）%, （28.30±0.27）% and （35.19±0.04）%, 0.05 ）. Combined arsenic trioxide and fenofibrate could ability of A549 cells with an invasive inhibition rate of respectively, in group B, group C and group D （P 〈 interference with the cell cycle and reduce the invasive （50.3±0.15）%, （56.7 ±0.57）% and （68.1±0.21 ） %, respectively, in group B, group C and group D （ P 〈 0. 05 ）. RT-PCR and Western blotting showed that the expression level of E-cadherin was significantly higher while the expression level of snail was significant- ly lower in group D than in groups A to C （P 〈 0. 05）. Conclusion Combined arsenic trioxide and fenofibrate exerts a significant effect on epithelial-interstitial transformation of A549 cells, which may be related with the expression of E-cadherin and Snail.

关 键 词：三氧化二砷 非诺贝特 肺肿瘤 上皮-间质转化 E-CADHERIN SNAIL 

分 类 号：R734.2[医药卫生—肿瘤]