KBP治疗子宫内膜异位症的作用和机制研究

We have reported that KBP inhibited growth of hepatocellular carcinoma and gastric carcinoma by anti-angiogenesis.Down-regulation of VEGF expression in tumor cells may represent a novel mechanism for the anti-angiogenic and anti-tumor activity of KBP.KBP suppressed LPS-induced TNF-a production via up-regulating SOCS3 expression in macrophages.Our previous study showed that KBP decrease in ectopic and eutopic endometrial tissues from endometriosis patients;KBP inhibit the growth of endometrial cells and induce apoptosis;KBP up-regulate SOSC3 in endometrial cells.The abnormal apoptosis of cells and angiogenesis are the important mechanisms of endometriosis.The previous report showed that higher expression of p-STAT-3 protein and lower expression of SOCS-3 protein in the ectopic endometrium of endometriosis patients compared with the eutopic and control endometria.SOSC3 negatively regulated STAT3 and the activation of STAT3 will stimulate the expression of VEGF and bcl-2 for angiogenesis and anti-apoptosis.So we will examine the inhibition of endometriosis in mouse models by KBP and investigate whether KBP inhibit STAT3,VEGF and bcl-2 through up-regulation of SOSC3 in endometrial cells.Our study could demonstrate that KBP suppresses growth of endometriosis and these results suggest that KBP could be a promising candidate and have therapeutic potential in endometriosis.

我们已报道KBP通过下调VEGF表达降低微血管密度抑制肝癌和胃癌生长；通过上调SOSC3表达抑制经LPS刺激巨噬细胞分泌TNF-a。预实验结果发现内异症子宫内膜中KBP含量下降；KBP抑制异位内膜细胞的生长诱导其凋亡，促进SOSC3的表达。子宫内膜细胞凋亡异常及血管增生是子宫内膜异位症重要的发病机制。已有研究发现内异症子宫内膜中SOSC3下降，STAT3表达升高。SOSC3是STAT3信号通路重要的负反馈调节因子，STAT3活化后能作为转录因子促进下游VEGF及bcl-2的表达，促进血管增生、抑制细胞凋亡。本研究拟在内异症动物模型上证实KBP抑制子宫内膜异位症的作用；细胞模型上探讨KBP是否通过SOSC3抑制STAT3活性，下调VEGF及bcl-2表达，明确KBP抑制子宫内膜异位症的分子机制。本项目旨在阐明KBP抗子宫内膜异位症的作用和机制，为治疗内异症提供候选药物和科学依据。

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