Toll样受体4促进非小细胞肺癌侵袭及氧化苦参碱干预作用的研究

项目名称： Toll样受体4促进非小细胞肺癌侵袭及氧化苦参碱干预作用的研究

项目编号： No.81503304

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡亚娥

作者单位： 南通大学

项目金额： 18万元

中文摘要： 肺癌尤其是非小细胞肺癌是我国发病率最高的恶性肿瘤。肺癌进展迅速、治疗效果差，极易复发和转移，是癌症患者死亡的主要原因。因此，研究肺癌侵袭、转移机制，寻找抗肺癌药物新靶点具有重要的研究意义和临床价值。Toll样受体4（TLR4）在其他肿瘤中起重要作用，但在肺癌侵袭和转移中的作用及机制尚未明确。我们之前的研究发现，中药单体氧化苦参碱具有抗肿瘤作用，我们想用于治疗肺癌，但缺乏直接证据。本项目前期结果显示，TLR4在肺癌组织中高表达；非小细胞肺癌细胞株A549和SPC-A-1在脂多糖刺激下，TLR4表达显著升高，同时其侵袭能力明显增强；氧化苦参碱能抑制肺癌细胞膜上TLR4的表达，减弱肺癌细胞的侵袭能力。本研究旨在通过体、内外实验研究揭示TLR4在肺癌侵袭和转移中的作用及机制，为预防和干预肿瘤侵袭和转移提供新的思路和治疗靶点，同时进一步阐明氧化苦参碱抗肿瘤机制，为其在抗肿瘤治疗中的应用提供依据。

中文关键词： Toll样受体4；非小细胞肺癌；氧化苦参碱；侵袭

英文摘要： In our country, lung cancer, especially non-small cell lung cancer, is of the highest incidence of malignancy and has following characteristics including rapid progress, poor prognosis, with high rates of recurrence and metastasis. It is the leading cause of cancer death. So it is important to uncover the mechanism of invasion and metastasis in lung cancer and to find new targets for therapy. It has reported that Toll-like receptor 4 (TLR4) plays crucial role in the development of other tumor, yet its effect and mechanism in the invasion and metastasis of lung cancer are still uncertain. Our previous study found that a traditional Chinese medicine oxymatrine has anti-tumor effect, but little direct evidence for the treatment of lung cancer. Our preliminary results are as follows: TLR4 is highly expressed in lung cancer tissues; LPS increases TLR4 expression on non-small cell lung cancer cells, A549 and SPC-A-1, as well as the invasive potential of the cells; Oxymatrine inhibits TLR4 expression on cells and reduces cell invasive potential. By in vivo and in vitro study, this project aims to reveal the mechanism of TLR4 in lung cancer invasion and metastasis, providing a new target for anti-tumor therapy. Meanwhile, further elucidating the anti-tumor mechanism of oxymatrine provides evidences for its application in anti-tumor therapy.

英文关键词： Toll-like receptor 4;non-small cell lung cancer;oxymatrine;invasion