珍珠梅黄酮纳米粒阻断STAT-3信号转导通路抑制肝癌细胞侵袭、转移作用的分子机制

信号转导和转录激活因子（STAT-3）是肿瘤发生、发展、转移、侵袭和扩散等生物学行为相关基因启闭的"总阀门"。TTF1是从抗癌中药珍珠梅中分离得到单体成分，TTF1纳米粒（TTF1-NP）是课题组采用乳化-低温固化法制备的新剂型。前期研究表明：TTF1-NP能显著抑制肝癌细胞STAT-3的穿核行为，降低STAT-3磷酸化水平，抑制STAT-3下游多种肿瘤转移侵袭相关因子的表达，推测TTF1-NP可能是通过调控STAT-3的转录活性来干预肿瘤细胞的侵袭、转移过程。本项目拟通过培养人肝癌细胞株和原代肝癌细胞、建立裸鼠移植瘤模型和DEN诱发原发性大鼠肝癌模型，采用分子生物学、激光共聚焦、EMSA和基因报告检测等方法，探讨TTF1-NP抑制STAT-3信号转导通路的作用靶点及通过何种途径抑制STAT-3转录活性，阐明TTF1-NP抗肝癌细胞侵袭、转移作用的分子机制，为肝癌治疗提供新的思路与靶点。

Signal transducer and activator of transcription 3 (STAT-3) is the main open and close valve of those genes related to the biological behaviors of tumor development, proliferation, metastasis and invasion. The Chinese medicinal herb Sorbaria sorbifolia is native to Changbai Mountain, and 5, 2′, 4′-trihydroxy-6, 7, 5′-trimethoxyflavone (TTF1) is the first monomeric compound identified from acetic ether extracts of Sorbaria sorbifolia. TTF1 nanoparticles (TTF1-NP) is a new dosage form prepared by the emulsification-evaporation method. Preliminary studies show that: TTF1-NP could significantly reduce STAT-3 phosphorylation levels in hepatoma carcinoma cells, and inhibit the expression of a variety of STAT-3 downstream tumor metastasis and invasion-related factors. In this study, we conducted in vitro and in vivo experiments by using human hepatoma cell line and primary liver cancer cells to establish the transplanted nude mice model and DEN-induced rat liver cancer model.And then,through aoptosis detection, molecular biology,RNA interference, confocal laser microscopy, EMSA and gene report detection methods and technologies, we explored TTF1-NP target of inhibition to STAT-3 signaling pathway and clarified the molecular mechanisms of TTF1-NP anti-hepatoma cell invasion, metastasis, which will provide new ideas and targets for the treatment of liver cancer, and provide theoretical and experimental basises for the development of Chinese herb Sorbaria sorbifolia.