探讨三氧化二砷(arsenic trioxide,As2O3)诱导胃癌细胞AGS的凋亡及对信号转导子与转录激活子基因(signal transducers and activators of transcription 3，STAT3)和血管内皮生长因子基因(vascular endothelial growth factor,VEGF)表达的影响。方法： 分别用1、5、10 μmol/L As2O3处理AGS细胞，在培养24、48、72 h后，以MTT法检测细胞的生长增殖,以流式细胞术和TUNEL法检测细胞凋亡,以ELISA、免疫组化和实时荧光定量PCR检测凋亡过程中相关基因STAT3、VEGF表达的变化。结果： （1）AGS细胞经As2O3作用后,细胞增殖受到明显抑制,且呈剂量和作用时间依赖关系；（2）FCM术检测在细胞周期G1期前出现亚二倍体凋亡峰；细胞周期分析显示G2/M期阻滞；（3）TUNEL标记发现DNA链的断裂；（4）在AGS细胞凋亡过程中， STAT3和VEGF表达下调，其中10 μmol/L浓度的As2O3作用最强。结论: As2O3抑制胃癌细胞AGS增殖并诱导凋亡,其机制可能与细胞周期阻滞和下调STAT3和VEGF基因表达有关。

To investigate the apoptosisinducing effect of arsenic trioxide (As2O3) on gastric carcinoma cell line AGS in vitro and to assess the influence of As2O3 on the expression of signal transducers and activators of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF). Methods: AGS cells were treated with different concentrations of As2O3 (1, 5, and 10 μmol/L) for 24,48, and 72 h. The cell proliferation was detected by MTT assay, cell apoptosis and cell cycle distribution were measured by flow cytometry and TUNEL, and the expression of STAT3 and VEGF was investigated by ELISA, immunohistochemistry and realtime PCR. Results: (1) As2O3 inhibited AGS cell proliferation in a time and dosedependent manner; (2) FCM results showed a typical subdiploid peak before G0/ G1 phase and cell cycle analysis showed G2/M phase arrest; (3) TUNEL analysis revealed the DNA fragmentation; (4) During the As2O3induced apoptosis of AGS cells, the expression of STAT3 and VEGF was downregulated, especially when As2O3 was at 10 mol/L. Conclusion: As2O3 can inhibit the proliferation of AGS cells and induce AGS cell apoptosis, which might be related with cell cycle block and downregulation of STAT3 and VEGF expression.

山东省科技攻关基金项目(No.2005GG3202171)