基于基膜聚糖—连环蛋白p120ctn探讨化痰祛瘀法干预肺癌转移的机制研究

转移是肺癌治疗失败和死亡的主要原因。中医学认为痰、瘀是肺癌转移的关键病机。前期临床研究证实具有化痰祛瘀功效的中药复方金福安汤能降低肺癌转移率、改善患者症状、提高生活质量。实验研究发现该方可抑制p120ctn异常表达介导减弱转录因子Kaiso的表达而干预肺癌细胞的迁移，并进一步在动物体内实验中得到证实。Lumican/p120ctn复合体在肺癌转移中起关键作用，其作用机制与中医理论的“痰、瘀”非常相似。结合前期研究，我们提出金福安汤可能通过促进lumican水平，上调Lumican/p120ctn复合体，阻断PI3K/Akt信号通路干预肺癌转移。本项目拟采用肺癌细胞株和肺癌移植瘤小鼠模型，运用基因干扰、外源基因表达及活体成像等技术，研究该方对lumican/p120ctn复合体及PI3K/Akt信号通路相关因子的影响，揭示该方干预肺癌转移的分子机制。研究结果将对中医药防治肺癌转移有重要意义。

Metastasis is the leading cause of death and treatment failure in the lung cancer patients, asthe focus and difficulty of current research. It is believed in the TCM theory that Phlegm and blood stasis are the key point of the invasion and metastasis in lung cancer. Previous clinical research have shown Jinfu’an decoction of dissipating phlegm and removing blood stasis, could stabilize tumor, reduce metastasis rate, improve clinical symptoms and improve quality of life. The experimental study reveals that the formula can inhibit the invasion and migration of lung cancer cell lines by inhibiting the abnormal expression of p120ctn by mediating down-regulating kaiso, proved by further studies on models of nude mouse with lung adenocarcinoma cell A549. Lumican/p120ctn complex plays a key regulatory role in lung cancer metastasis, and its mechanism is closely related to the “Phlegm ” and “ blood stasis” of the TCM theory. We propose that Jinfu’an decoction can up-regulate the p120ctn and mediate p120ctn/Lumican complex by promoting the expression of lumican, thereby blocking the PI3K/Akt signaling pathway to prevent lung cancer metastasis, based on the former study. This project intends to test the lumican, lumican/p120ctn complex and PI3K/Akt signaling pathway in vitro and in vivo experiments, by using gene interference, exogenous gene expression and living imaging and so on , in lung cancer cell lines and lung cancer nude mous models. And we can further reveal the molecular mechanism of the formula intervention of lung cancer metastasis.