基于凝集素芯片与凝集素亲和层析技术的参芪扶正注射液联合 IFN-α对肝癌切除术后复发转移干预机制的糖蛋白组学研究

Hepatocellular carcinoma (HCC) is a high-grade malignant cancer. Moreover, postoperative recurrence and metastasis are the major cause of low therapeutic efficiency and poor prognosis for HCC patients, and are closely related to the glycosylation and expression of glycoproteins. Previous research in our lab has shown that the combination of Shenqi Fuzheng Injection (SFI) and IFN-α has great potential in inhibiting the invasion of HCC cells. However, the effects of such combination on the glycosylation and expression of glycoproteins in HCC cells remain to be investigated. Based on the lectin array and lectin affinity chromatography, in vivo and in vitro experiments are designed to screen, validate and analyze the differential glycosylation patterns and the differential profilings of characteristic lectins-affinity glycoproteins using HCC tissues of nude mice treated with SFI and IFN-α, alone or in combination respectively compared to control groups. Molecular mechanisms of SFI and IFN-α, alone or in combination functioning in the characteristic glycosylation will be also verified by experiments on nude mice and HCC cells. This systematic glycoproteomics analysis is aimed to explore the inhibitory mechanism of postoperative recurrence and metastasis of HCC by SFI and IFN-α combination based on the expression of glycosyltransferase, the alteration of glycosylation, the expressions and functions of differential glycoproteins, which is possible to provide new ideas for the prevention of postoperative recurrence and metastasis of HCC, and is also valuable for achieving significant progress in the research and clinical treatment of Chinese medicine.

肝癌的恶性程度极高，肝癌切除术后复发转移作为提高肝癌疗效与生存率的巨大障碍，与诸多糖蛋白的糖基化修饰及表达水平密切相关。实验室的前期工作表明，小剂量参芪扶正注射液联合IFN-α可显著抑制肝癌细胞侵袭，但对其糖蛋白糖基化修饰及表达水平的影响尚待探究。本项目将基于凝集素芯片与凝集素亲和层析技术，通过裸鼠模型实验和细胞实验，对比对照组结果，筛选、验证并解析参芪扶正注射液与IFN-α单独及联合应用组肝癌组织糖蛋白差异糖基化修饰谱及特定糖基化修饰差异糖蛋白谱，并验证单独及联合用药影响肝癌组织及细胞糖蛋白特定糖基化修饰的分子机制。项目将从糖基转移酶转录表达水平、糖基化修饰的变化及特定糖基化修饰差异糖蛋白的表达和功能等不同层面，系统的进行参芪扶正注射液联合IFN-α对肝癌切除术后复发转移干预机制的糖蛋白组学研究，可为防治肝癌切除术后复发转移提供新的思路，对促进中药研究与临床治疗均具有重要意义。

肝癌的恶性程度极高，肝癌切除术后复发转移作为提高肝癌疗效与生存率的巨大障碍，与诸多糖蛋白的糖基化修饰及表达水平密切相关。本研究借助凝集素芯片以及凝集素亲和层析串联生物质谱定量分析技术，结合循环肝癌细胞复发转移小鼠模型，获得了益气扶正法代表药物之参芪扶正注射液与IFN-α联合应用组肝癌组织及血清糖蛋白差异糖基化修饰谱和特定糖基化修饰差异糖蛋白谱；通过体内外实验结合生物信息学分析，由对糖基转移酶催化作用的影响、糖基化修饰的变化以及特定糖基化修饰差异糖蛋白的表达和功能等不同层面，初步探索了参芪扶正注射液联合IFN-α干预肝癌复发转移的可能机制，为防治肝癌切除术后复发转移提供了新的思路，对促进中药研究与临床治疗均有意义。

内容获取失败，请点击重试