三氧化二砷对胃癌MGC803细胞增殖和凋亡作用的研究

目的研究三氧化二砷（As2O3）对人体外胃癌细胞株MGC803细胞生长周期和相关凋亡基因表达的影响,进一步探讨As2O3作用机制和多耐药性原因。方法将不同浓度三氧化二砷作用于MGC803细胞株后体外培养,应用流式细胞仪（FCM）分析各组细胞周期变化,Westblotting观察相关凋亡基因Bcl-2和Caspase3增殖变化。结果 As2O3为0.5μmol/L时,S期细胞分布（32.41±2.11）（对照组28.24±1.38）,G2/M期细胞分布（31.28±0.19）（对照组30.05±0.18）两者比较差异无统计学意义（P〉0.05）,当As2O3浓度为1.5μmol/L时,S期细胞分布（33.55±2.37）,G2/M期细胞分布（27.74±0.46）,与对照组比较,差异有统计学意义（P〈0.05）,药物提高到2.5μmol/L时,S期细胞分布（41.03±2.37）,G2/M期细胞分布（19.15±0.46）,与对照组比较,差异有统计学意义（P〈0.05）;westblotting显示As2O3能同时下调Bcl-2,上调Caspase3蛋白的表达而诱导细胞凋亡。结论三氧化二砷能够使胃癌MGC803细胞的S期细胞逐渐增多,G2/M期减少,从而抑制细胞增殖,同时能减少Bcl-2和增加Caspase3蛋白的表达,促进肿瘤细胞的凋亡和延缓耐药性的发生,所以在临床应用As2O3化疗时要注意药物的有效浓度以及掌握好化疗周期,以尽可能提高疗效的同时减轻不良反应,延缓耐药性的发生。

The Effect of Arsenic Trioxide（As_2O_3） on the Proliferation and Apoptosis of Gastric Cancer MGC803 Cell Line

Objective To study the effect of arsenic trioxide（As2O3） on the growth cycle and apoptosis-related gene expression of human gastric cancer MGC803 cell line and further discuss the effect mechanism of As2O3and the causes of multi-drug resistance.Methods MGC803 cells cultured in vitro were lines influenced by different concentrations of arsenic trioxide. The changes of cell cycle of all the groups were analyzed by flow cytometry（FCM）. And the proliferative changes of the relevant apoptotic genes Bcl-2and Caspase3 were observed by westblotting. Results When the concentration of As2O3 was 0.5 渭mol/L, distribution of S phase was32.41卤2.11, and distribution of G2/M phase was 31.28卤0.19 and there were no statistical differences（P0.05） between the groups as compared with those of the control group（distribution of S phase： 28.24卤1.38; distribution of G2/M phase： 30.05卤0.18）. When the concentration of As2O3was 1.5 渭mol/L, distribution of S phase was 33.55 卤2.37, and distribution of G2/M phase was 27.74 卤0.46; there were statistical differences between the groups as compared with those of the control group（P0.05）. When the drug concentration increased to 2.5 渭mol/L, distribution of S phase was 41.03 卤2.37, distribution of G2/M phase was 19.15 卤0.46 and there were statistical differences between the groups as compared with those of the control group（P0.05）. Westblotting showed that As2O3could induce apoptosis of cells by downregulating the expression of Bcl-2 and upregulating the expression of Caspase3.Conclusion Arsenic trioxide can inhibit the proliferation of gastric cancer MGC803 cell line by increasing S phase cells and decreasing G2/M phase cells. Meantime, it can promote tumor cell apoptosis and delay drug resistance occurring by decreasing the expression of Bcl-2 and increasing the expression of Caspase3 protein. Therefore, effective concentration of As2O3and the right chemotherapy cycle in clinical application should be emphasized, as far as possible to improve the efficacy of As2O3, alleviate the side effects and postpone the occurrence of drug resistance.