摘要
铂类配合物5a是从200多个新合成的铂类配合物中筛选得到。该文旨在研究其对多种肿瘤细胞的体外抗肿瘤作用,对正常细胞的毒性,同时对其抗肿瘤作用机制进行初步探讨。采用CCK8试剂盒检测5a对不同来源的肿瘤细胞的抑制作用。用透射电子显微镜观察5a作用后人结肠癌细胞HCT-116形态的变化。采用流式细胞术检测细胞凋亡及细胞内活性氧水平的变化,并通过Western blot检测相关凋亡蛋白表达。结果显示5a可以抑制多种肿瘤细胞的增殖,呈剂量依赖性。透射电镜和流式细胞术检测结果表明,5a能诱导HCT-116发生凋亡,并使细胞内活性氧水平显著提高。5a作用后的HCT-116细胞呈现典型凋亡特征,并促使细胞色素C从线粒体释放到胞浆内,从而激活Caspase-9。总之,配合物5a在体外显示了良好的抗肿瘤活性,有成为一种新一代铂类抗癌药物的潜能,并能诱导HCT-116细胞发生内源性凋亡。
Compound 5a,cis-（trans-lR,2R-diaminocyclohexane） bis （2-tert-butoxyacetate） platinum （II） was screened from a chemical pool containing more than 200 platinum analogues. Here, the antitumor activity of 5a against various human tumor cells in vitro was studied and its cytotoxieity against human normal tissues was also investigated. The underlying mechanism was also initially elucidated. Here,Cell Counting Kit-8 was used to determine the inhibitory effect of 5a against tumor cells. Morphological changes of HCT-116 cells were observed by transmission electron microscopy. Apoptosis and cellular reactive oxygen species （ROS） level were evaluated by Flow Cytometry （FCM） analysis. Western blotting assay was used to detect the expression of several apoptosis-related proteins. The data showed that 5a inhibited viability of various tumor cells in a dose-dependent manner. The results of transmission electron microscopy and Flow eytometry showed that 5a could trigger apoptosis and increased cellular ROS level dramatically in HCT- 116 cells. As typical apoptosis events were observed in 5a treated cells, cytochrome C in mitochondrion eventually leaked into cyto- plasm, directly activated caspase-9. In conclusion,5a exhibited superior cell growth inhibition activity in vitro, and it could activate intrinsic apoptosis in HCT-116 cells ,which might serve as a potent novel platinum drug against cancer in future.
出处
《药物生物技术》
CAS
2013年第6期500-504,共5页
Pharmaceutical Biotechnology
关键词
5a
铂类药物
抗肿瘤
HCT-116细胞
细胞凋亡
线粒体
活性氧簇
5a, Platinum compounds, Antitumor, Hct-116 cells, Apoptosis, Mitochondrion, Reactive oxygen species （ros）
