摘要
目的初步研究胞嘧啶核苷卟啉与DNA(ctDNA)相互作用及抗肿瘤活性。方法人体生理条件下(pH=7.4),利用紫外光谱法和荧光光谱法初步研究胞嘧啶核苷卟啉与小牛胸腺DNA的相互作用。采用MTT法,替加氟为阳性对照药,以肝癌细胞Bel-7402、宫颈癌细胞Hela、乳腺癌细胞MCF-7为测试细胞株对胞嘧啶核苷卟啉抗肿瘤活性进行检测。结果实验发现,胞嘧啶核苷卟啉[T(p-CH3)PPO-Cytidine]与DNA相互作用使紫外-可见光谱发生了6 nm的红移,并出现了明显的减色效应。荧光光谱强度明显减少,吸收峰位发生变化。初步体外抗癌活性实验结果表明,胞嘧啶核苷卟啉对肝癌细胞Bel-7402、宫颈癌细胞Hela、乳腺癌细胞MCF-7的抑制率呈剂量依赖性,随着浓度的增加抑制强度逐渐增大。结论胞嘧啶核苷卟啉对DNA发生了作用且可能形成了配合物,通过卟啉结构单元的引入可以明显提高胞嘧啶核苷的抗肿瘤活性。
Objective To study DNA-bing and anti-tumor activity of cytidine-bonded porphyrins.Methods The interaction of T（p-CH3） PPO-Cytidine synthesized in our laboratory with ctDNA was investigated by UV spectrum and fluorescence spectrum under physiological conditions（pH = 7.4） for the first time.Their anti-tumor avtivities against cancer cell line Bel-7402,Hela and MCF-7 were tested by MTT,with tegafur positive control.Results Addition of DNA resulted in obvious hypochromism and bathochromic of 6 nm in the absorption spectra.A significant reduction in the fluorescence spectra was also observed.The in vitro antitumor activity test showed that the cellular inhibitory rate of T（p-CH3） PPO-Cytidine against cancer cell line Bel-7402,Hela and MCF-7 was calculated respectively,indicating the inhibition was dose-dependent and increased with concentration.Conclusion T（p-CH3） PPO-Cytidine may interact with DNA.At the same time,they may become new complexes.In vitro antitumor activity test shows that the synthesized compounds are the potential anti-cancer agent.The antitumor activity of cytidine may be improved obviously by binding a porphyrin block.
出处
《中南药学》
CAS
2013年第6期401-404,共4页
Central South Pharmacy
基金
国家自然科学基金(No.20502005)
湖南省重点科技项目(No.2008GK2023)
