金雀异黄素增加胃癌BGC-823细胞对5-氟尿嘧啶敏感性的研究

Sensitization of human gastric cancer cell line BGC-823 to 5-fluorouracil by genistein

目的:研究金雀异黄素(genistein,Gen)对5-氟尿嘧啶(5-fluorouracil,5-FU)抑制BGC-823胃癌细胞活性的影响。方法:Gen与5-FU单独及联合作用于胃癌BGC-823细胞24、48及72h后,采用MTT法测定细胞的活性;Gen与5-FU单独及联合处理胃癌BGC-823细胞72h后,透射电镜观察细胞超微结构改变,免疫细胞化学法研究凋亡相关基因的蛋白Bcl-2和Bax的表达。结果:20件μmol/LGen和10μmol/L 5-FU联合应用对胃癌细胞的生长导致了更显著的增殖抑制作用(P<0.01);Gen、5-FU单独及联合应用均可诱导BGC-823细胞凋亡;Gen、5-FU联合应用时对BGC-823细胞的凋亡相关蛋白Bcl-2表达下调和Bax表达上调的作用较单独时明显(P<0.05)。结论:金雀异黄素可能通过上调Bax的表达和下调Bcl-2的表达而增加BGC-823细胞的凋亡,增加5-FU的抗癌活性。金雀异黄素是一种无毒的抗癌药,其与5-FU合用于胃癌患者可能提高化疗的效果。有必要开展金雀异黄素和5-FU合用的临床试验来检验该假设。

Objective：To investigate the effect of genistein（Gen）on antitumor activity of 5-fluorouracil（5-FU）on BGC-823gastric cancer cells.Methods：BGC-823cells were treated with Gen（20μmol/ L）,5-FU（10μmol/L）and their combination treatment for 24,48hand 72h,respectively.Then,MTT assay was employed to measure the cell viability.Furthermore,BGC-823cells were treated with Gen and 5FU,single or dual agents for 72h,the ultramicrostructure changes of cancer cells were observed under transmission electron microscopyand the alterations in expression of Bcl-2and Bax were examined by immunocytochemistry assay.Results：The combination of 20μmol/L genistein and 10μmol/L 5-FU resulted in significantly greater viability inhibition（P0.01）.Gen and 5-FU,utilized singly or in combination,could induce apoptosis and down-regulate the expression of Bcl-2or up-regulate the expression of Bax of BGC-823cells.In addition,the dual agents utilized in combination,the alterations in expression of Bcl-2 and Bax were more significant（P0.05）.Conclusions：The results in the present study suggest that genistein could enhance the activity of 5-FU via up-regulation the expression of Bax and down-regulation the expression and enhancing apoptosis of cancer cells.Genistein is a promising nontoxic agent that may enhance chemotherapy outcome in gastric cancer patients when given concomitantly with 5-FU.Clinical trials of Gen and 5-FU combination are warranted to test this hypothesis.