中文摘要
联合应用抗血管生成拟态(VM)治疗是改善抗肿瘤血管生成治疗效果欠佳的有效措施。基于毒生病络理论,我科在肿瘤治疗的过程中,采用通络及阻络的方法,辨证施治,取得了较好的临床效果。因此,从中药中筛选并开发具有抑制VM的抗癌新药具有重要的意义。前期研究发现,马钱子碱具有潜在的抗血管生成的作用,能明显抑制乳腺癌的血管生成。本项目在前期研究工作的基础上,以TRPS1为切入点,探讨TRPS1在马钱子碱抑制乳腺癌细胞血管生成及VM过程中的作用,并阐明马钱子碱通过靶向TRPS1调控下游VEGF/EphA2/VE-cadherin/MMPs信号通路的效应与机制。通过建立乳腺癌动物模型,观察马钱子碱对乳腺癌生长、转移的抑制作用,并验证马钱子碱抑制乳腺癌血管生成及VM的分子机制。本项目研究成果,不仅为马钱子碱抑制乳腺癌血管生成及VM的机制进行理论上的新探索,更重要的是为开发生物利用度高的抗癌新药奠定基础。
英文摘要
Combining application of anti-angiogenesis and anti-vasculogenic mimicry is an effective measure to reduce the mortalit and morbidity breast cancer. Based on the theory of abnormal collaterals, we believe that inhibition of anti-vasculogenic mimicry might prove to be a promising strategy for restraining tumor progression in breast cancer. It was very important to develop new drugs that anti-angiogenesis and anti-vasculogenic mimicry from Chinese traditional medicine which has the function of inhibiting abnormal collaterals. Previous studies was performed to investigate the inhibitory effects of Brucine on inhibition of angiogenesis in breast cancer. It was reported that the functions of TRPS1 in angiogenesis may provide a promising target for breast cancer treatment.Therefore, in our study, we explored the role of TRPS1 in Brucine-mediated inhibition of angiogenesis in vivo. We also investigated the VEGF/EphA2/VE-cadherin/MMPs signaling pathway in inhibition of asculogenic mimicry and angiogenesis in breast cancer cells. These findings reveal that application of Brucine in treating angiogenesis and vasculogenic mimicry boasts promising prospect and will become potential therapy all over the world.
