中文摘要
肝细胞癌(HCC)是世界范围内最常见且恶性度最高的肿瘤之一, 其发病与HBV感染密切相关。分子靶向治疗药物是近年来治疗癌症的新宠。研究表明, TLR7介导抗病毒免疫应答,对其配体的识别需要脂筏提供信号平台启动免疫调节,而脂筏微区紧密结合的脂质有利于TLR7-MyD88寡聚蛋白复合物的形成。这些数据强调了脂筏在调节TLR7信号通路的重要性。以扶正培本法作为肝癌的基础治疗方法在提高人体抗病能力,帮助机体抵御和祛除病邪方面显示了较好的临床疗效。本研究旨在阐明以扶正培本法作为肝癌基础治疗方法的分子机制,以人参皂苷aPPD为工具药,分别通过人体生物标本、体外细胞培养和肝癌小鼠模型,研究TLR7蛋白在脂筏区表达量、位置分布的变化和结构功能的异常,调控肝癌病人TLR7的功能,探索基于脂筏调节TLR7表达治疗肝癌的分子机制,为肝癌治疗提供新的药物靶点。
英文摘要
Hepatocellular carcinoma (HCC) is one of the most common and highest malignant tumor in the world. The onset of HCC is closely related to hepatitis B virus (HBV). Molecular targeted therapy has become the rising focus on treatment of cancer in recent years. Studies have shown that toll-like receptor 7 (TLR7) can mediate the antiviral immune response. The ligand recognition of TLR7 needs lipid rafts to provide the signal platform to start the immunoregulation. The tightly bound lipids in raft-microdomains benefit the formation of TLR7-MyD88 oligomeric protein complexes. These data emphasize the importance of lipid rafts in regulating TLR7 signaling pathway. Fu Zheng Pei Ben therapy as the basic treatment of improving immunity and removing pathogeny in HCC has shown a better clinical efficacy. This study aims to clarify the molecular mechanisms of lipid rafts regulating TLR7 expression on HBV-infected HCC treatment with Fu Zheng Pei Ben. Through the analysis of changes of TLR7 protein expression, distribution and structure in lipid rafts after aPPD treatment, explore the molecular mechanisms of Fu Zheng Pei Ben therapy and provide a new drug target for HCC treatment.
