脾虚内环境Oatp表达对肝癌CSC“干性”及PTEN/AKT信号通路影响研究

脾虚内环境与肝癌发生发展关系密切。前期研究中，我们发现脾虚内环境有机阴离子转运肽(Oatp)表达是机体内环境变化的重要原因,进一步研究发现脾虚小鼠肝癌组织Oatp表达异常与肝癌发生发展关系密切。我们预实验发现脾虚小鼠肝癌组织肿瘤干细胞（CSC）CD133表达明显升高,而CSC是导致肿瘤发生发展的重要因素，我们推测脾虚内环境Oatp异常表达可能与CSC在肝癌发生发展所起作用密切，提出“脾虚内环境Oatp表达变化--肝癌CSC‘干性’相关”假说。为证实这一假说，我们将建立脾虚肝癌小鼠模型，以脾虚内环境Oatp表达变化为切入点,通过检测脾虚肝癌小鼠和对照肝癌小鼠CD133＋CSC的自我更新能力、增殖能力、迁移侵袭能力和成瘤能力等，同时检测肝癌CSC相关PTEN/AKT信号转导通路变化，探讨脾虚内环境Oatp表达变化对肝癌CSC“干性”影响的分子机制，促进中医藏象理论和湿浊转运理论的完善和发展。

The environment of spleen deficiency is closely related to the occurrence and development of hepatocellular carcinoma (HCC). In previous studies, we found the expression of organic anion transporter (OATP)in spleen deficiency environment was one of the most important reasons for environmental changes in the body, further study found that abnormal expression of OATP in mice with spleen deficiency is closely related to the occurrence and development of HCC. Our preliminary experiments found that the expression of CD133 in HCC mice with spleen deficiency was significantly increased, which has been identified as cancer stem cell (CSC) of HCC. As we all know, the CSC is an important factor in the occurrence and development of tumor, we therefore hypothesized that the abnormal expression of OATP in spleen deficiency environment might be closely related to function of CSC in occurrence and development of HCC. So we hypothesized that the expression of OATP in spleen deficiency environment might be closely related to the characteristic of CSC of HCC. To confirm this hypothesis, we will build of hepatocellular carcinoma models in mice with spleen deficiency, the OATP expression changes in spleen deficiency being as the breakthrough point, the CD133+ CSC self renew differentiation ability, proliferation, migration invasion and tumorigenicity will be detected in HCC mice with spleen deficiency, and detection of hepatocellular carcinoma stem cells PTEN/AKT signal transduction pathway f CSC will also be detected in the same time. Fuether explore the molecular mechanism of OATP expression in spleen deficiency environmental on the characteristic of CSC, provide new therapeutic strategies for TCM in prevention and treatment of HCC, as well as promote improvement and development the theory of TCM in turbid transport and transformation.