三氧化二砷对神经母细胞瘤细胞Trk基因家族表达的影响  

Effect of Arsenic trioxide on the expression of Trk family in neuroblastoma cells

作　　者：黎阳[1] 熊稀霖[1] 亓凯[1] 刘玲[2] 陈月琴[3] 张驰[1] 郭海霞[1] 方建培[1] 薛红漫[1] 

机构地区：[1]中山大学孙逸仙纪念医院,儿童血液/肿瘤专科,广东广州510120 [2]广东医学院附属医院儿童医学中心,广东湛江524000 [3]中山大学生命科学学院,广东广州510120

出　　处：《中华肿瘤防治杂志》2016年第17期1149-1153,共5页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的神经母细胞瘤(neuroblastoma,NB)是儿童常见的实体瘤,三氧化二砷(Arsenic troxide,As_2O_3)现已广泛应用于治疗实体肿瘤,为了探讨As_2O_3治疗NB的可行性,本研究检测As_2O_3对人SK-N-SH细胞周期及Trk基因家族表达的影响。方法通过流式细胞术检测4μmol/L浓度的As_2O_3作用48h后SK-N-SH细胞细胞周期的变化;qRT-PCR法检测As_2O_3在1、2和4μmol/L浓度下对SK-N-SH细胞分别作用24和48h后,对SK-N-SH细胞内TrkA、TrkB和TrkC基因表达的影响。结果用4μmol/L As_2O_3作用48h后,SK-N-SH细胞的G2/M期细胞比例为(30.93±0.34)%,而对照组G_2/M期细胞比例为(5.29±0.23)%,两组间差异有统计学意义,P<0.01。1μmol/L As_2O_3作用SK-N-SH细胞24h的TrkA比值为1.43±0.17,48h为3.88±0.26,两者比较差异有明显统计学意义,P<0.01,但随着As_2O_3浓度继续增大至4μmol/L TrkA反而下调。SK-N-SH细胞的TrkB及TrkC基因表达均随着As_2O_3浓度增加而上调,4μmol/L浓度下与对照组比较差异有统计学意义(P<0.05),48h比24h上调更明显。结论初步研究结果表明,As_2O_3不仅对NB的SK-N-SH细胞有明显杀伤作用,使其阻滞在G_2/M期,还能使与NB预后密切相关的Trk基因的表达发生变化,As_2O_3有用于NB治疗的潜在临床价值。OBJECTIVE Neuroblastoma is a common childhood tumor. Arsenic trioxide （As2O3）, a drug has been used in a variety of cancer cell types, including certain solid tumors. The aim of this study was to confirm As2O3 influence on cell cycle of SK-N-SH cells and gene expression of TrkA, TrkB and TrkC. METHODS SK-N-SH cells were cultured first, and then the cell cycle of SK-N-SH cell treated with 4μmol/L As203 for 48 h were examined by flow cytometry a- nalysis. The genes TrkA, TrkB and TrkC expression were determined by Real-time RT PCR. The cells were cultured in three different concentration divided into the experimental 1 μmol/L, 2μmol/L, 4μmol/L groups and the control group, for 24 h and 48 h respectively. RESULTS Treatment of the SK-N-SH cells with 4 μmol/L As2O3 for 48 h resulted in a significant accumulation of cells in G2/M phase （30.93±0. 34） % compared with the untreated cells （5.29±0.23） %, P〈0.01. TrkA level increased in cells treated 1 μmol/L As2O3 for 48 h to a greater degree than those treated for 24 h （P〈0.01）. TrkA was downregulated by 2 μmol/L and 4 μmol/L As2O3. With increasing concentration of As2O3, the expression levels of TrkB and TrkC were all significantly upregulated, especially at 48h compared with 24 h, although their expressions at both time points were significantly higher than that of the control （P〈0.01）. CONCLUSION The results suggested that to treat stage 1 ,stage 2 and stage 4S NB, which have a good prognosis and high expression of TrkA and TrkC, the concentration and treatment time of As2O3 should be increased, to treat stage 3 and stage 4NB, which have a bad prognosis and high expression of TrkB, an appropriate concentration and treatment time of As2O3 should be carefully determined.

关 键 词：神经母细胞瘤 Trk基因家族 三氧化二砷 细胞周期 化疗 

分 类 号：R739.4[医药卫生—肿瘤]