目的 观察三氧化二砷(As2O3)对人肿瘤坏死因子相关凋亡诱导配体(TRAIL)抑制人肺癌A549细胞增殖作用的影响及机制.方法 体外培养A549细胞至对数生长期后随机分为As2O3组、TRAIL组、联合组及对照组,As2O3组分别加入1、10 μmol/L As2O3,TRAIL组加入100 μg/L TRAIL,联合组分别加入1 μmol/L As2O3+100 μg/L TRAIL 、10 μmol/L As2O3+100 μg/L TRAIL,对照组加入DMEM培养液.四组均继续培养24、48、72 h,采用四甲基偶氮唑蓝(MTT)比色法检测细胞生长情况,计算细胞增殖抑制率(IR);用RT-PCR法检测死亡受体4(DR4)mRNA、死亡受体5(DR5)mRNA表达变化.结果 联合组IR显著高于As2O3组及TRAIL组,尤以作用48 h和72 h为著(P均＜0.05);联合组DR4 mRNA和DR5 mRNA表达均明显强于As2O3 组及TRAIL组(P均＜0.05).结论 As2O3 可增强TRAIL对A549细胞增殖的抑制作用,机制可能为上调DR4 mRNA和DR5 mRNA表达;此为肺癌的临床靶向治疗提供了依据.%Objective To investigate the effect of arsenic trioxide on the inhibiting proliferation against A549 cells roles of TRAIL and the possible mechanism. Methods The A549 cells were cultured to logarithmic phase in vitro and divided into As2O3 group, TRAIL group, combined group and the control group, then the As2O3 group were treated with As2O3 of 1,10 μmol/L ,the TRAIL group was treated with TRAIL of 100 μg/L, the combined group was treated with 1 μmol/L As2O3 + 100 μg/L TRAIL and 10 μmol/L As2O3 + 100 μg/L TRAIL respectively, the control group was given DMEM. The 4 groups were continuely cultured for 24,48,72 hs, MTT method was used to detect inhibition ratio (IR) to A549 proliferation. DR4 and DR5 mRNA level of A549 cells were detected by RT-PCR . Results Compared with the As2O3 group and TRAIL group ,the IR in the combined group increased significantly,especially higher after the treatment of 48 h and 72 h ( all P ＜ 0.05 ); the expression of DR4 and DR5 mRNA in combined group were obviously higher than those in As2O3 group and TRAIL group(all P＜0. 05). Conclusions As2O3 can enhence TRAIL inhibits of human lung cancer cell line A549 growth by inducing death receptor 4 and 5 gene levels in vitro; the result provided a reasonable basis for targeting therapy of lung cancer.
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