消癌平注射液(XAP)是中药通关藤的制剂，前期工作表明该药能显著改善非小细胞肺癌(NSCLC)对吉非替尼(gefitinib)的耐药。耐药除与有关信号通路异常表达相关外，还与CYP450酶介导的药物代谢特征改变有密切联系，使药物浓度降低，药效下降。gefitinib在体内主要经肝药酶CYP3A4和CYP2D6代谢。预试验表明XAP能抑制CYP450酶对gefitinib的代谢，显著降低该酶对gefitinib的清除率；耐药NSCLC患者血中gefitinib浓度较低，联合XAP能提高其血药浓度。因此，本项目拟研究XAP在体内、外对gefitinib代谢的影响；探讨gefitinib和代谢产物浓度变化与其疗效之间的关系；阐明XAP通过调控CYP450代谢酶而改善gefitinib耐药的可能机制。这些工作将为应用XAP克服gefitinib耐药提高临床疗效提供科学依据,具有重要的现实意义。

XiaoAiPing injection (XAP) is a prepareation from the extract of Marsdenia tenacissima. Our previous work showed that XAP significantly restored gefitinib sensitivity in resistant NSCLC cells and xenograft mouses models. It is shown that drug resistance is not only related to the abnormal expression of some signaling pathways, but also to cytochrome P450 (CYP450) mediated drug metabolism. The low drug level in blood and tumor tissue, the decreased drug efficacy was observed. Gefitinib is mainly metabolized by CYP3A4 and CYP2D6 enzymes. Our preliminary test showed that XAP inhibited gefitinib metabolism in recombinant human CYP450 enzymes by reducing the clearances of gefitinib. Furthermore, the combination of XAP increased plasma gefitinib concentration in resistant NSCLC patients. Therefore, the present project intends to study the effect of XAP on gefitinib metabolism in vitro and in vivo,and to explore the correlation between gefitinib resistant related signaling pathways, gefitinib concentration, and the efficacy. The possible mechanisms of XAP overcoming gefitinib-resistant by regulating CYP450 enzyme activities will also be clarified. In whole, the present research will provide scientific evidence for using XAP to restore gefitinib sensitivity and to improve its clinical efficacy.