摘要
背景与目的:水杨醛氨基酸Schiff碱基本结构中含C=N键,当其与金属离子配位后生物活性增强,表现出一定的抗癌、抑菌等活性。本研究主要探讨4种水杨醛氨基酸Schiff碱铜配合物(6B、7B、6P、7P)对人胃癌细胞株BGC823增殖的影响,并初步探讨其作用机制。方法:取对数生长期的BGC823细胞传代培养,24h后加药,MTT法测定4种配合物对BDC823细胞生长的影响;流式细胞仪检测细胞凋亡及细胞周期变化;DNAladder试验检测DNA损伤;免疫细胞化学法检测P53蛋白表达水平。结果:MTT实验结果:不同种类的水杨醛氨基酸Schiff碱铜配合物对BGC823细胞的生长均有明显的抑制作用,并且随配合物浓度的增大抑制作用有增强的趋势。4种配合物对BGC823细胞的IC50分别为6B18.10μmol/L,7B27.50μmol/L,6P3.61μmol/L,7P3.45μmol/L。流式细胞仪检测表明4种铜配合物均可明显提高BGC823细胞凋亡率,DNAladder试验也证实这一点;流式细胞仪检测还揭示铜配合物引起S期细胞和G2期比率增加,G1期细胞减少;P53蛋白免疫细胞化学染色显示,4种配合物均能够下调BGC823细胞突变型P53蛋白的表达,提示细胞凋亡的发生与p53依赖的凋亡通路有关。结论:配合物6B、7B、6P、7P在体外均能明显抑制肿瘤细胞BGC823生长增殖,诱导细胞凋亡,并造成细胞周期分布的改变。其机制可能与p53依赖的凋亡通路有关。
Background and Objective： The basic structure of salicylaldehyde-amino acid Schiff base compounds includes a C=N chemical bond. These compounds show significant antitumor activities in vitro when combined with a metal ion. This study investigated the effects and possible mechanisms of four salicylaldehyde-amino acid Schiff base copper ternary coordination compounds on the proliferation of human gastric cancer cell line BGC823. Methods： The BGC823 cells were treated with the four compounds （6B,7B,6P,and 7P）. Cell proliferation was detected by MTT assay. Apoptosis and changes in the cell cycle were analyzed by flow cytometry. DNA damage was observed using a DNA ladder assay. The expression of p53 protein was determined by immunocytochemistry. Results： The proliferation of BGC823 cells was significantly inhibited by the four compounds and the effect was concentration-dependent. The half maximal inhibitory concentration （IC50） of 6B,7B,6P,and 7P for BGC823 cells were 18.10,27.50,3.61,and 3.45 μmol/L,respectively. Flow cytometry showed the four drugs induced apoptosis in BGC823 cells,which was confirmed by DNA ladder experiments. Flow cytometry also detected changed phases in the cell cycle from treatment with the compounds. The percent of cells in the G0/G1 phase decreased and that of cells in the G1/S and G2/M phases increased,indicating that S- and G2-phase blockages exist. As shown by immunocytochemistry,the expression of p53 decreased in BGC823 cells treated with the four drugs,indicating the involvement of the p53 pathway to BGC823 cell apoptosis. Conclusions： The four compounds showed significant activities on restraining proliferation of BGC823 cells in vitro,induced apoptosis,and caused changes in the cell cycle. This may be related to the downregulation of p53.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2010年第3期298-303,共6页
Chinese Journal of Cancer
