基于SDF-1/CXCR4生物轴介导CAFs调控肺癌转移作用机制探讨臭牡丹黄酮类化合物干预作用

肿瘤微环境在肺癌转移中发挥着重要作用，肿瘤相关成纤维细胞(CAFs)是肺癌微环境中最主要的基质细胞，能重塑肿瘤微环境，作用于邻近的肿瘤细胞促进转移。趋化因子SDF-1及其受体CXCR4组成的SDF-1/CXCR4生物轴是CAFs与肿瘤细胞发生交互作用的信使，能介导CAFs促进肺癌迁移、黏附、侵袭。我们发现臭牡丹黄酮类化合物能有效干预肺癌转移，推猜其解毒散瘀之功效在于改善肿瘤微环境，基于其具有抗炎抗肿瘤药理作用，本研究以趋化因子SDF-1作为切入点，体外建立CAFs和A549共培养体系，体内采用A549-GFP混合CAFs注入裸鼠体内的方法建立裸鼠肺癌移植瘤模型，观察臭牡丹黄酮类化合物对肿瘤细胞的侵袭转移力的影响和SDF-1/CXCR4轴的调控机制，以阐明臭牡丹黄酮类化合物干预肺癌转移的作用机理。

Tumor microenvironment plays an important role in lung cancer metastasis.Tumor associated fibroblasts (CAFs) which is the main stromal cells in lung cancer microenvironment can restore the tumor microenvironment and act on the adjacent tumor cells to promote transfer. The SDF-1 / CXCR4 biological axis is the messenger of CAFs and tumor cell interactions, can be mediated CAFs promote lung migration, adhesion and invasion.With the Clerodendrum bungei flavonoids has an effective intervention in lung cancer metastasis, We speculate its effect of Detoxification and scattered stasis is to improve the tumor microenvironment. With pharmacological effects in anti-inflammatory and anti-tumor of Clerodendrum bungei flavonoids, the study take SDF-1 as a breakthrough point, establish CAFs and A549 co-culture system in vitro, and the A549 -GFP mix CAFs injected into nude mice to establish nude mouse lung transplantation tumor model in vivo, with the Clerodendrum bungei flavonoids intervention, to observe the the influence on invasion and metastasis of tumor cells and the regulatory mechanism of SDF-1/CXCR4 axis, to clarify intervention mechanism of Clerodendrum bungei flavonoids in lung cancer metastasis.