从Cyr61调控上皮间质转化角度探讨清胰化积方抗胰腺癌肝转移作用的分子机制

肝转移是胰腺癌预后差和主要致死原因之一，目前也缺乏有效的治疗手段。课题组临床研究发现以清胰化积方为主治疗胰腺癌肝转移患者疗效显著优于对照组；实验研究也揭示该方能抑制胰腺癌细胞肝转移生长以及下调Cyr61，但其作用机制还有待进一步探讨。故此，我们提出假说:"湿热毒聚"是胰腺癌发病的核心病机和转移的关键, 针对该病机的清胰化积方抗胰腺癌肝转移作用可能通过下调Cyr61逆转EMT表达。为了验证该假说，我们拟通过人胰腺癌高肝转移细胞SW1990HM以及原代细胞和肝转移裸小鼠模型，采用Real time PCR、Western blot、慢病毒载体和RNA干扰等手段，在分子、细胞、组织和动物整体水平上观察清胰化积方作用Cyr61调控EMT表达，明确该方抗肝转移作用的分子机制。本研究将从Cyr61调控EMT这个新视点为揭示中药复方抗胰腺癌肝转移的作用机制奠定基础，为中药治疗肿瘤转移提供新思路和新方法。

Liver metastasis prognosis is poor and the main death cause of pancreatic cancer，lack of effective treatment now. Group clinical study found that pancreatic cancer with liver metastasis patients treated by Qingyihuaji formula are significantly better than the control group；experimental study also revealed that qingyihuaji formula inhibit the growth of liver metastasis of pancreatic cancer cells and down-regulate Cyr61,but its mechanism remains to be further explored. Therefore,we propose a hypothesis:"hot and humid poison accumulation " is the core of pancreatic cancer pathogenesis and the key of metastasis, liver metastasis of pancreatic cancer treated by Qingyihuaji formula maybe down-regulate Cyr61 and reverse EMT expression. To test this hypothesis, we intend to use high liver metastatic cell SW1990HM as well as primary cell and nude mouse liver metastasis model,using Real time PCR,Western blot,lentiviral vector and RNA interference methods,to observe Qingyihuaji formula affecting Cyr61 regulation of EMT expression on the molecular,cellular,organization and the overall animal level, clear the molecular mechanism of anti-tumor metastasis. From the new point of view of the Cyr61 regulation of EMT, this study lay the foundation for revealing the mechanism of liver metastasis of pancreatic cancer treated by Chinese herbal compound, and provide new idea and new method of anti-tumor metastasis of Chinese medicine.