前期研究发现清胰化积方具有逆转胰腺癌耐药作用，在EphB2高表达癌细胞中更明显，联合干预抑制肿瘤相关巨噬细胞（Tumor-associated Macrophages，TAMs）M2型极化并降低胰腺癌干细胞比例。最新研究显示炎性微环境与胰腺癌耐药关系密切，TAMs是重要炎性细胞，M2型TAMs通过EphrinB1-EphB2轴促进微血管异常生成降低药物浓度和敏感性诱发耐药。据此提出假说：清胰化积方通过EphrinB1-EphB2轴抑制TAMs M2型极化促进微血管正常增加癌细胞内药物浓度和抑制癌干细胞恶性转化增加药物敏感性发挥作用。项目建立不同EphB2表达人胰腺癌细胞，体内建立原位接种模型，体外建立癌细胞、血管内皮细胞和M2型TAMs共培养模型，通过明确EphrinB1-EphB2轴介导的TAMs M2-M1转化、微血管正常、抑制胰腺癌干细胞转化与逆转耐药关系揭示清胰化积方发挥作用机理。

Our Previous studies found that Qingyihuaji formula(QYHJ) reversed the drug resistance of pancreatic cancer which was more obvious in EphB2 high expression pancreatic cancer cells. QYHJ jointed intervention with Gemcitabine inhibited M2-type polarization of tumor associated macrophages (TAMs) and reduced pancreatic cancer stem cell ratio. The latest research shows that inflammatory microenvironment closely related with pancreatic cancer drug resistance, TAMs are important inflammatory cells, M2 type TAMs induced drug resistance by promoting microvascular abnormalities to generate lowering drug concentration and sensitivity through EphrinB1-EphB2 axle. We put forward our hypothesis according to the above results: QYHJ reverse pancreatic cancer drug resistance by suppressing TAMs M2-type polarization which can promote microvascular normalization to increase drug concentration in pancreatic cancer cells and inhibit cancer stem cells malignant transformation to increased drug sensitivity through EphrinB1-EphB2 axis. This project will establish different EphB2 expression human pancreatic cancer cells, create pancreas orthotopic model established in vivo, build co-culture model of pancreatic cancer cells, endothelial cells and M2-type TAMs in vitro,and reveal the mechanism of reverting drug resistance of QYHJ by explicating the relationship of QYHJ mediated TAMs M2-M1 transformed, microvascular normalization, inhibition of pancreatic cancer stem cells malignant transformation through EphrinB1-EphB2 axis.