摘要
目的:研究金雀异黄素(Genistein,Gen)与5-氟尿嘧啶(5-fluorouracil,5-FU)联合应用对人胃癌细胞BGC-823的生长抑制是否具有协同作用及其可能的作用机制。方法:MTT法检测Gen、5-FU单独及联合对BGC-823细胞生长的抑制作用并用中效原理定量分析两药合用的剂量-效应关系。Gen、5-FU单独及联合处理BGC-823细胞72 h后,流式细胞术检测细胞周期分布的变化,并在透射电镜下观察细胞超微结构的改变。结果:Gen、5-FU单用或联合应用对BGC-823细胞的生长均有显著的增殖抑制作用且呈剂量和时间依赖性。两药联合应用时,当药物效应(抑制率)大于50%时,具有协同作用[合用指数(Combination index,CI)≤1];6.06 mg/L Gen作用72 h后,95.74%的BGC-823阻滞在G2/M期;1.23 mg/L 5-FU作用72 h后,G0/G1及S期细胞分别为58.26%和41.59%,0.81 mg/L Gen与1.01 mg/L 5-FU联合应用72 h后,67.99%的BGC-823细胞阻滞在G0/G1期。Gen、5-FU单独或联合均可诱导BGC-823细胞凋亡。结论:Gen和5-FU单独或联合应用,均对BGC-823细胞具有抑制增殖的作用,在一定浓度范围内,Gen与5-FU联合应用对胃癌细胞的增殖具有协同抑制作用,Gen与5-FU可能通过阻滞细胞周期和诱导细胞凋亡而抑制胃癌细胞的生长。该研究为Gen与5-FU可能联合用于胃癌的治疗提供了依据。
Objective:To investigate whether combined application of Genistein(Gen)and 5-fluorouracil(5-FU)exerts synergistic effect on growth inhibition of human gastric carcinoma cells BGC-823 and their possible mechanisms in vitro.Methods:Human gastric carcinoma cell line BGC-823 was exposed to Gen and 5-FU exclusively or in combination at different concentrations for 24,48 h and 72 h.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay was employed to investigate the inhibitory effect of Gen and 5-FU,exclusively or in combination on BGC-823 cells.Furthermore,method of median-effect principle was utilized to quantitatively analyze the dose-effect relationship of the combined effects of Gen and 5-FU.Then,BGC-823 cells were exposed to Gen and 5-FU,exclusively or in combination for 72 h,the ultramicrostructure changes of cancer cells were observed by transmission electron microscopy(TEM)and the distribution of cell cycles was detected by flow cytometry(FCM).Results:Combined or exclusive application of Gen and 5-FU exerted significant inhibitory effect on the proliferation of BGC-823 cells in both time and dose dependent manner.When inhibition rate(IR)exceeding 50%,combined application of Gen and 5-FU displayed synergistic effect on growth inhibition of BGC-823 cell line.Being exposed to 6.06 mg/L Gen,1.23 mg/L 5-FU and 0.81 mg/L Gen combined with 1.01 mg/L 5-FU for 72 h,95.74% BGC-823 cells were arrested at G2/M phases,58.26% and 41.59% BGC-823 cells were arrested at G0/G1 and S phases and 67.99% BGC-823 cells were arrested at G0/G1 phases,respectively.Gen and 5-FU,used exclusively or in combination,could induce apoptosis and arrest cell cycle of BGC-823 cells.Conclusions:Combined or exclusive application of Gen and 5-FU can suppress the proliferation of BGC-823 cells in vitro.Through arresting cell cycle and inducing cell apoptosis,combined application of Gen and 5-FU can inhibit the growth of BGC-823 cells.Combined application of Gen and 5-FU exerts synergistic effect on growth of human gastric carcinoma cells within certain range of concentration.The study provides evidences for the potential combined application of Gen and 5-FU in the treatment of human gastric cancer.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2012年第12期1053-1058,共6页
Journal of Chongqing Medical University