肝癌术后复发转移是癌症患者高死亡率的主要原因，尚无有效防治方法。传统抗肝癌复发转移化疗药物毒副作用大且安全系数低。我们前期研究显示：高效低毒的熊果酸及其衍生物(UAs)体外具有较好抗肝癌细胞粘附迁移能力，并可抑制肝癌细胞和血管内皮细胞表面粘附因子表达；体内可有效减少小鼠黑色素瘤肺转移，提示其具有抗肿瘤转移潜力；进一步基因芯片技术发现其对肝癌细胞粘附信号通路有显著影响。综上本项目提出UAs可干预肝癌转移关键步骤的新设想，拟从分子-细胞-动物水平研究其干预肝癌细胞与血管内膜粘附作用及机制。包括：研究药物对细胞表面粘附分子、血小板和刺激因子等影响；探索药物干预肝癌细胞与血管内膜粘附的作用及机制；阐明药物干预肝癌细胞粘附转移作用特点及其量效-时效关系；揭示药物抗肝癌转移的可能机制及分子靶点。本项目将为UAs在肝癌血行转移源头步骤中的干预作用提供重要科学依据，为肝癌复发转移早期防治探讨新策略。

Tumor recurrence and metastasis is the leading cause of liver cancer mortality. There is no effective method so far to prevent recurrence and metastasis of tumor. Traditional anti-cancer drugs for the treatment of hepatoma metastasis have high toxic side effects and low safety factor. Our previous study showed that ursolic acid and its derivatives (UAs) could lead to a signi?cant reduction of hetero-adhesion of HepG2 cells to human umbilical vein endothelial cell (HUVEC) in vitro, reduce HepG2 cell migration in a wound-healing assay, inhibit the expression of adhesion molecules on HUVEC. In addition, UAs suppressed experimental lung metastasis of mouse melanoma B16-F10 cells in vivo. Moreover，GeneChip studies showed that UAs had a significant impact on the cellular focal adhesion pathway in HepG2 cells. These results revealed the potential of UAs for hepatoma metastasis chemoprevention. Therefore, we proposed the new idea that UAs may interfere with the initial step of cancer metastatic cascade. In this project, we will further investigate the interference effect of UAs on the adhesion of hepatoma cells with vascular endothelium and reveal its mechanisms on both a molecular, cellular and animal level, which includes: To demonstrate the interaction with UAs, cell adhesion molecules, platelets and cytokines; To explore the interference effect and mechanism of UAs with hetero-adhesion of hepatoma cells to vascular endothelium; To clarify the characteristics and seek the relations of time-effect and dosage-effect by using UAs for restraining hepatoma cells from initial metastatic cascade; Furthermore, the possible mechanisms of UAs inhibits hepatoma metastasis and underlying molecular targets will be revealed. This study will provide an important scientific basis for the intervention effect of UAs in the key step of liver cancer hematogenous metastasis, and explore a new strategy for the early prevention of hepatoma metastasis.