摘要
目的:设计合成高分子基多胺抗癌药物(三乙烯四胺基淀粉,CTS),研究其对人端粒DNA d[G3(T2AG3)3]的作用机制和细胞毒性,提供高分子靶向抗癌药物的另一种开发思路。方法:以三乙烯四胺为出发点,通过环氧氯丙烷为桥梁连接到廉价淀粉上获得化合物CTS,通过各种光谱手段对CTS进行表征,运用圆二色CD光谱研究其与人端粒DNA的相互作用机制,采用CCK-8方法研究CTS对人眼脉络膜黑色素瘤(OCM-1)细胞的抑制作用。结果:CTS可以诱导人端粒DNA形成反平行G-四链体,对于OCM-1细胞具有较强的毒性,可以抑制其生长,而CTS对正常的人视网膜色素上皮(ARPE-19)细胞毒性极低,表明CTS可以作为以G-四链体为靶点的癌细胞潜在的靶向药物。结论:CTS可以促进G-四链体的生成,并对OCM-1细胞具有较强的抑制性,而对正常细胞影响微小。
Objective:To design and synthesize the potential antitumor drug,CTS(triethylenetetramine-starch).Its interactions with the human telomere DNA(d[G3(T2AG3)3 series])and cytotoxicity to OCM-1 tumor cells are investigated.As a consequence,it provides a new strategy to develop targeted antitumor drugs.Methods:The triethylenetetramine reacted with the epichlorohydrin crosslinked-starch(CS)to produce the CTS.It was characterized by various methods.The circular diehroism(CD)spectra were used to clarify the interaction mechanism between the CTS and human telomere DNA.Its cytotoxity to OCM-1 cells was determined by CCK-8 method.Results:The antiparallel G-quadruplex could be induced and stabilized by CTS.This may be the reason that CTS inhibited the growth of OCM-1 cells,and moreover it showed very low cytotoxicity to ARPE-19 human cells.Such observations indicated that CTS was a promising antitumor drug.Conclusion:The CTS can stabilize the G-quadruplex and has higher cytotoxicity to OCM-1 cells.It has insignificant effects on the growth of normal human cells.
作者
程如梅
步叶旭
CHENG Rumei;BU Yexu(School of Ophthalmology&Optometry,Wenzhou Medical University,Institte of Advanced Materials for Nano-Bio Appli-cations,Wenzhou,325027)
出处
《温州医科大学学报》
CAS
2016年第1期19-23,共5页
Journal of Wenzhou Medical University
基金
国家自然科学基金资助项目(21405115)
浙江省医药卫生科研项目(2015KYB254)
温州市科技局科技计划项目(Y20120218)
温州医科大学附属眼视光医院项目(YNCX201408)
