CAJ | 학술논문

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,24 h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;DNA ladder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IC_(50)分别为6B 18.10 μmol/L,7B 27.50 μmol/L,6P 3.61 μmol/L,7P 3.45 μmol/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,DNA ladder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G_2期比率增加,G_1期细胞减少;P153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.
배경여목적:수양철안기산Schiff감기본결구중함C=N건,당기여금속리자배위후생물활성증강,표현출일정적항암、억균등활성.본연구주요탐토4충수양철안기산Schiff감동배합물(6B、7B、6P、7P)대인위암세포주BGC823증식적영향,병초보탐토기작용궤제.방법:취대수생장기적BGC823세포전대배양,24 h후가약,MTT법측정4충배합물대BDC823세포생장적영향;류식세포의검측세포조망급세포주기변화;DNA ladder시험검측DNA손상;면역세포화학법검측P53단백표체수평.결과:MTT실험결과:불동충류적수양철안기산Schiff감동배합물대BGC823세포적생장균유명현적억제작용,병차수배합물농도적증대억제작용유증강적추세.4충배합물대BGC823세포적IC_(50)분별위6B 18.10 μmol/L,7B 27.50 μmol/L,6P 3.61 μmol/L,7P 3.45 μmol/L.류식세포의검측표명4충동배합물균가명현제고BGC823세포조망솔,DNA ladder시험야증실저일점;류식세포의검측환게시동배합물인기S기세포화G_2기비솔증가,G_1기세포감소;P153단백면역세포화학염색현시,4충배합물균능구하조BGC823세포돌변형P53단백적표체,제시세포조망적발생여p53의뢰적조망통로유관.결론:배합물6B、7B、6P、7P재체외균능명현억제종류세포BGC823생장증식,유도세포조망,병조성세포주기분포적개변.기궤제가능여p53의뢰적조망통로유관.
Background and Objective:The basic structure of salicylaldehydeamino 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 concentrationdependent.The half maximal inhibitory concentration(IC_(50))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 G_0/G_1 phase decreased and that of cells in the G_1/S and G_2/M phases increased,indicating that S-and G_2-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.