侵袭和转移是胰腺癌主要死因和治疗难点，课题组提出"湿热毒聚"是胰腺癌发病的核心病机和侵袭转移内因。研究证实，针对该病机组方的清胰化积方治疗转移性胰腺癌临床疗效显著优于常规化放疗；该方可抑制胰腺癌高转移细胞系的体内生长和肝转移灶形成。Rho GTP酶激活蛋白(ARHGAP)家族参与肿瘤侵袭、细胞周期、TGF-β等通路，与肿瘤转移密切相关。然而该家族与胰腺癌关系尚未阐明。课题组预实验中:1.高通量筛选实验证实胰腺癌与癌旁组织ARHGAP表达差异显著;2.基因集富集分析提示ARHGAP4可能参与胰腺癌侵袭转移多条通路;3.清胰化积方治疗后胰腺癌患者外周血ARHGA4表达升高。清胰化积方是否通过ARHGAP抑制胰腺癌侵袭转移？其参与的机制如何？本研究拟从体内外实验观察清胰化积方抑制胰腺癌侵袭转移、调控ARHGAP和下游转移相关信号通路的作用，探索清胰化积方抗胰腺癌侵袭转移的作用机制。

Invasion and metastasis are main reasons of death for pancreatic cancer. Treatment for invasion and metastasis of pancreatic cancer is of great difficulty in clinical practice. The research group put forward that accumulation of damp, heat, and toxicity is the core pathogenesis of pancreatic cancer and the basis of invasion and metastasis. Clinical researches indicated that the anti-tumor effect of Qingyihuaji (QYHJ) formula in combination with conventional treatment such as chemotherapy or radiotherapy was significantly better than the latter alone. Experimental studies revealed that QYHJ formula could inhibit the growth of high liver metastasis potential human pancreatic cancer cells, and decrease the formation of liver metastatic lesions. Rho GTPase activating protein (ARHGAP) family is involved in signaling pathways such as tumor invasion, cell cycle, and TGF-β pathway, etc. The family is highly correlated with the evolution of tumor metastasis. However, the relationship between invasion or metastasis of pancreatic cancer and ARHGAP family is not well understood. Our preliminary research indicated the following facts: 1. High throughput screening experiment combined with the third party database authentication showed that the expression of ARHGAPs in pancreatic cancer tissue was highly different from that of the para-carcinoma tissue. 2. Gene Set Enrichment Analysis illustrated that ARHGAP family may participate in multiple cell signaling pathways in correlation with invasion and metastasis of pancreatic cancer. 3. After treatment of Qingyihuaji formula, the expression of ARHGA4 in peripheral blood of the pancreatic patients was significantly increased. Is the inhibition of invasion and metastasis in pancreatic cancer caused by QYHJ formula related to regulation of ARHGAP family? What is the mechanism underlying? To answer the questions, the project plans to investigate the effect of QYHJ formula in vivo and in vitro, and the regulation of Rho GTPase-activating protein family and its downstream biological molecular signals. The aim of the research is to explore the mechanism of QYHJ formula in inhibition of invasion and metastasis of pancreatic cancer.