全反式维甲酸联合顺铂对A549细胞增殖及Bcl-2和P53基因表达的影响  

All-trans retinoic acid promote chemical sensitivity of cisplatin on A549 cells and function on expression of Bcl-2 and P53 genes

作　　者：刘红[1] 李伟国 张国瑞[1] 李海燕[3] 吴志伟[1] 位亚静 陈红杰[1] 王静[1] 

机构地区：[1]郑州大学第一附属医院呼吸与危重症医学二科,450052 [2]伊川县人民医院神经内二科,471300 [3]郑州大学第五附属医院老年呼吸科,450052

出　　处：《国际呼吸杂志》2015年第19期1446-1450,共5页International Journal of Respiration

基　　金：河南省科技厅项目[（JH02）：102300410249]

摘　　要：目的探讨全反式维甲酸（ATRA）联合顺铂（DDP）对肺癌A549细胞增殖、凋亡的影响及其可能机制。方法MTT法观察ATRA和／或DDP对A549细胞增殖的抑制作用；流式细胞仪检测不同药物干预后A549细胞的凋亡率；免疫细胞化学方法检测各组Bcl-2及野生型P53基因的表达情况。结果①MTT结果显示，ATRA组、DDP组及ATRA＋DDP组的吸光度值均明显降低。②AnnexinV／PI双染法流式细胞术检测显示，ATRA组、DDP组、ATRA＋DDP组细胞的凋亡率明显高于对照组，ATRA组细胞的凋亡率高于DDP组。③免疫细胞化学结果显示，ATRA组、DDP组及ATRA＋DDP组Bcl-2表达降低，密度及深度均减弱；ATRA、ATRA联合DDP作用于肺癌A549细胞后，P53表达增高，ATRA＋DDP组P53表达进一步增高。结论ATRA对肺癌A549的增殖具有抑制作用，ATRA能促进肺癌细胞凋亡，且具有时间依赖性；与DDP联合应用可增加后者的抑制作用；ATRA和／或DDP联用，能促进P53基因表达，抑制Bcl-2基因表达。Objective To explore the effect and possible mechanism of all-trans retinoic acid （ATRA） combind cisplatin （DDP） on proliferation, apoptosis of lung cancer A549 ceils. Methods The inhibition functions of ATRA with/or DDP on cancer cells was tested by MTT method. Apoptosis ratio of A549 cells in four groups was detected by flow cytometry. The expression of Bcl-2 and wild-type p53 gene in four groups was detected by immunohistochemical mothod. Results （1）MTT results showed that the absorbance values of the ATRA group, ATRA＋DDP group and DDP group were significantly lower. （2） The results of Annexin V/PI double staining flow cytometry showed that the cell apoptosis rate of ATRA group,DDP group and ATRA--DDP group was significantly higher than that of control group, respectively. The cell apoptosis rate of ATRA group was higher than that of DDP group. （3）The results of immunohistochemistry showed that compared to the control group, the expression of Bcl-2 gene was decreased in ATRA group,DDP group and ATRA＋ DDP group, both density and depth were weakened. The expression of P53 gene was increased in ATRA group and ATRA＋DDP group. Compared to ATRA group,the expression of P53 gene in ATRA＋DDP group was increased further. Conclusions ATRA can inhibit proliferation, promote apoptosis on lung cancer A549 cells, which renders time-dependent. The inhibition rate and apoptosis rate of ATRA on A549 ceils can be increased if combined with DDP. ATRA combined with DDP can promote the expression of P53 gene,and inhibit the expression of Bcl-2 gene.

关 键 词：全反式维甲酸 顺铂 肺癌 凋亡 BCL-2 P53 

分 类 号：R135.1[医药卫生—劳动卫生]