Malignant tumor is a serious public health problem all over the world. One of the most important and hottest spots in the field of tumor research is exploration of new drug with anti-tumor effect. CD47 is a drone which has been reported to possess the activity in interfering in the interaction of CD47-SIRPa. Therefore, screening inhibitor of CD47 becomes to be a hot topic in the development of anti-tumor drug. Natural products resource is a large treasure for exploration of CD47 inhibitor. The inhibitors from natural products may increase the effect of chemo-treatment. And it will be very significant in explanation on the theory of synergy and atenuation of Traditional Chinese Medicines (TCMs) when combined with chemical medicines against tumor. Based on a novel cell membrane chromatographic column acting on CD47 studied in our preliminary research, a 2-methacryloyloxyethyl phosphorylcholine (MPC) cell membrane affinity chromatography (CMAC) online-high performance liquid chromatography/mass spectrometry (HPLC/MS) method will be developed in this study for screening CD47 binding components from TCMs. A traditional herbal medicine of Curcuma wenyujin with exact anti-tumor effect wil be used as an example for validation the method and screening the CD47 binding components which may against liver cancer. Many techniques such as CMAC online HPLC/MS system, high speed counter current chromatography and medium pressure liquid chromatography will be used in screening, isolation and purification of CD47 binding components. Finally, the obtained components will be test and verified for their anti-tumor activity. Our research aims to excavate some anti-cancer drugs with high targeting, effective and low toxicity from TCMs. Moreover, the development of this platform will provide a powerful model in transformation of theory to application of cell membrane chromatography, and offer a new pathway for the pharmacodynamic material basis study of TCMs.
恶性肿瘤是世界严重的公共卫生问题,积极开发防治恶性肿瘤的新型药物是当今肿瘤研究的重点和热点。CD47是一个针对性干扰CD47-SIRPa相互作用的靶标,CD47抑制剂的筛选已成为抗肿瘤药物研究的热点课题。从天然产物中寻找CD47抑制剂,对提高癌症化疗疗效,解释中药的增效减毒效应十分重要。本项目拟以CD47受体为靶标,立足前期研究的一种新型细胞膜亲和色谱柱,构建羟乙基磷酰胆碱细胞膜亲和色谱在线液相色谱-质谱联用系统,以结构多样、活性良好的传统中药温郁金为对象,利用细胞膜色谱在线液质联用、高速逆流色谱、中压柱色谱等技术对CD47结合成分进行初步筛选、分离、鉴定,同时还将对筛选到的结合成分进行抗肿瘤活性验证,从温郁金中为肝癌的有效治疗挖掘一些靶向、高效和低毒的药物。同时,该技术平台的建立,也将为细胞膜亲和色谱技术的转化研究提供一个有力范例,为中药药效物质基础的研究提供一条新的思路。
CD47是细胞表面一个重要的"self"标记,是一个针对性干扰CD47-SIRPa相互作用的靶标,其抑制剂的筛选已成为抗肿瘤药物研究的热点课题。从巨大的天然产物库中寻找CD47抑制剂,前景广阔。本项目以CD47受体为靶标,通过对聚合溶液中致孔剂与单体组成、功能单体与交联剂组成、致孔剂组成比例、细胞破碎度、细胞用量等参数的优化,创新性地建立了一种新型细胞膜亲和色谱柱,通过对构建羟乙基磷酰胆碱细胞膜亲和色谱在线液相色谱平台对温郁金中的CD47结合成分进行筛选,筛选到两个结合成分,并进行抗肿瘤活性验证。同时,我们建立了新型的微提取-含量测定方法对温郁金类药材进行质量分析,并基于络合反应研究了一种以高速逆流色谱快速有效分离β-榄香烯的工艺。该研究有效地从温郁金中为肝癌的治疗挖掘到了一些靶向、高效和低毒的小分子成分。此外,该技术平台的建立,也为细胞膜亲和色谱技术的转化研究提供一个有力范例,为中药药效物质基础的研究提供一条新的思路。在本课题的资助下,共发表SCI研究论文7篇,申请国家发明专利3项,培养硕士生5名。
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数据更新时间:2023-05-31
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