三氧化二砷联合5-FU体外抗人胃癌细胞SGC-7901作用及机制的研究

Anti-tumor Effect and Mechanism of Arsenic Trioxide in Combination with Fluorouracil on Human Gastric Cancer Cell Line SGC-7901 in vitro

目的:探讨三氧化二砷(As2O3)与5-氟尿嘧啶(5-FU)联合应用体外抗人胃癌细胞株SGC-7901的作用及其机制。方法:用不同浓度的As2O3(终浓度依次为0.1,0.5,1.0μmol/L)和(或)5-FU(终浓度50mg/L)处理SGC-7901细胞后,采用流式细胞术观察细胞凋亡和细胞周期变化;免疫细胞化学法(PV法)观察凋亡相关基因Bcl-2表达的变化。结果:与As2O3或5-FU单药作用相比,As2O3与5-FU联合应用可显著提高诱导胃癌细胞凋亡率(q=63.9608,166.1758,51.3343,P<0.01),与空白组相比,联合用药后S期细胞所占比例下降(q=16.0743,10.8805,12.1482,P<0.01),G0/G1期细胞比例上升(q=8.7188,9.3309,9.8534,P<0.01),癌细胞Bcl-2基因表达明显下降(q=10.2801,17.8456,19.0086,P<0.01)。结论:As2O3与5-FU联合应用具有协同抗胃癌作用,其机制可能与细胞周期阻滞、增强诱导胃癌细胞凋亡以及调控凋亡相关基因的表达有关。

Objective： To study the anti-tumor effects of arsenic trioxide combined with fluorouracil on human gastric cancer cell line SGC-7901 in vitro and the mechanisms of the regimen. Methods： The human gastric cancer cell line SGC-7901 was treated n vitro using As2O3 （final concentrations in order： 0.1, 0.5, 1.01μmol/L） and 5-FU （final concentration： 50mg/L） respectively alone or in combination, then the cell apoptosis rate and phases of cell cycle were determined by flow cytometry, and the expression of Bcl-2 was analyzed by immunocytochemical method （PV method）. Results： Compared with As2O3 or 5-FU groups, As2O3 combined with 5-FU obviously increased the apoptosis rate of SGC-7901 （q=63.9608, 166.1758, 51.3343, P〈0.01）. Compared with blank group, the cell cycle distribution was altered and the ratio of S phase cell decreased （q=16.0743, 10.8805, 12.1482, P〈0.01）and G0/G1 phase increased （q=8.7188, 9.3309, 9.8534, P〈0.01）. After intervened by As2O3 combined with 5- FU, the expression of Bcl-2 was down-regulated （q=10.2801, 17.8456, 19.0086, P〈0.01）. Conclusion： As2O3 combined with 5-FU has the synergistic effects on SGC-7901, and the mechanisms may be related to cell cycle blocking and apoptosis-inducing effects through regulating the expression of the related genes.