脑胶质瘤耐药是国内外研究热点，目前临床上尚缺乏逆转脑胶质瘤耐药的有效药物。千层纸素是中药黄芩的有效成分之一。本课题组前期研究表明，千层纸素可透过血脑屏障，在体内外具有显著的逆转脑胶质瘤替莫唑胺耐药作用。肿瘤相关星形胶质细胞是脑胶质瘤微环境中重要组份，并通过间隙连接通道介导脑胶质瘤耐药。我们研究发现千层纸素可抑制肿瘤微环境中间隙连接通道的活性和间隙连接蛋白Cx43的表达，同时可抑制耐药细胞中Wnt/β-catenin信号通路的激活。本课题将着眼于肿瘤微环境，揭示微环境中间隙连接蛋白Cx43在脑胶质瘤耐药过程中的作用，以及Cx43是否通过Wnt信号通路介导脑胶质瘤耐药，基于此阐明千层纸素逆转脑胶质瘤耐药的确切机制。目前相关研究尚未见报道。此课题将为脑胶质瘤耐药的研究提供新思路，为临床脑胶质瘤的精准治疗提供理论基础和候选药物。

Drug resistance of glioma has been the focus of cancer research, but no effective reversal agent is now available in clinical treatment. Oroxylin A is one of the effective components of Scutellaria baicalensis Georgi. Our previous study showed a promising reversal effect of oroxylin A on glioma in vivo. Moreover, oroxylin A could pass blood brain barrier (BBB) and break the gap junction of astrocytes and glioma cells in tumor microenvironment. The preliminary results showed that oroxylin A could suppress the gap junction protein Cx43 as well as Wnt/β-catenin signal pathway. This research will focus on tumor microenvironment and aim at elucidating the functions of Cx43 and Wnt signal pathway in glioma drug resistance, thus shed some light on the mechanism of oroxylin A’s reversal effect on drug resistance. This research will provide new strategies and candidate agents for precise clinical treatment of glioma resistance.