摘要
目的:本实验研究了两种新型铂(Ⅱ)类配合物(2,3-吡啶二羧酸二水合铂、2,3-吡嗪二羧酸二水合铂)对结肠癌SW620细胞系的体外抗癌活性及其对细胞凋亡的影响。同时与奥沙利铂作一对照,以明确该两种新型铂(Ⅱ)类配合物是否具有更好的体外抑瘤效果。方法:采用人结肠癌细胞系SW620作为研究对象,三种药物分别以不同浓度作用于对数生长期的SW620细胞24h、48h后,应用软琼脂糖集落形成试验检测集落形成抑制率,以Annexinv/PI双染法测定细胞凋亡率,以扫描电镜观测三种药物作用后细胞形态和超微结构的改变。结果:软琼脂糖细胞集落形成抑制率实验显示出奥沙利铂、吡嗪、吡啶三种药物做用24h后对SW620细胞系的半数抑制浓度(IC_(50))分别为266.51,176.18,159.25μmol/L,48h的IC_(50),分别为158.84,161.27,125.67μmol/L,其药物作用强度为吡啶>吡嗪>Oxa,有显著性差异(P<0.01)。AnnexinV/PI双染法显示出三种药物均可诱导SW620细胞产生凋亡,其作用呈浓度和时间依赖性,并且随药物作用浓度及时间延长死亡细胞增多,作用强度为吡啶>吡嗪>Oxa,有显著性差异(P<0.01)。电镜下可见细胞典型早晚期细胞凋亡特征。结论:这两种新型铂(Ⅱ)配合物对结肠癌SW620细胞系显示出良好的体外抑瘤效果,该作用呈浓度和时间依赖性,并且强于奥沙利铂。药物作用靶点之一在于诱导细胞产生凋亡。
Abstract Objective： The aim of our study was to identify the in vitro antitumor activity of two novel Platinum （Ⅱ） com plexes against SW620 cell line, describe the effect of the two drugs on cell apoptosis, and compare the depressant effects of the two new drugs with those of oxaliplatin. Methods： The human colon carcinoma cell line SW620 was used as the research object. Three antitumor agents, oxaliplatin, pyrazine and pyridine, of different concentrations, were administered to the SW620 cell line at logarithmic growth phase for 24 and 48 hours, respectively. The colony inhibition ratio was then determined using human tumor cloning assay （soft-agarose colony formation test）. Cell apoptosis was assayed by means of Annexin V-FITC binding assay. Changes in morphology and ultra-structure after administration of the three drugs were observed by scanning electron microscopy. Results： In human tumor cloning assay, after the SW620 cells were treated with oxaliplatin, pyrazine and pyridine for 24 hours, the half inhibiting concentration （IC50） was 266.51, 176.18 and 159.25μmol/ L, respectively. And 48 hours after the administration of the three drugs, the IC50 was 158.84, 161.27 and 125.67μmol/L, respectively. The strength of drug action, from high to low, was pyridine, pyrazine and then oxaliplatin, with significant differen＇ces among the three （P〈0.01）. In the Annexin V-FITC binding assay, our data indicated that all of these drugs can induce apoptosis of the cell line SW620, with concentration and time dependence in the drug action. Cell death increased as the concentration augmented and the time of drug action extended. The order for the intensity of drug action can be listed from high to low as follows： pyridine, pyrazine and oxaliplatin, with significant differences among the three （P〈0.01）. By scanning electron microscopy, typical morphological changes of apoptosis were observed. Conclusion： Based on the results of this study, we conclude that the two new type platinum （ Ⅱ ） complexes have demonstrated a satisfactory in vitro anti-tumorous effect on the colon cancer cell line SW620. The drug action of the chemotherapeutic agents presents concentration and time dependency and the efficacy of the drugs are higher compared to oxaliplatin. Finally, we conclude that one of the targets in the drug action is induction of cell apoptosis.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第17期965-969,共5页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金资助(编号:20671064)~~
