理冲生髓饮有效组分药物血清通过JAK/STAT信号通路对卵巢癌血管生成影响的机制研究

Aggressive ovarian cancer neovascularization, by sprouting of endothelial cells, promotes host angiogenic factors ( such as VEGF) releasing and then cause the cancer cell endothelial activative. Studies have shown that STAT3 in the JAK / STAT signaling pathway, can directly regulate the transcription of VEGF and inhibite the expression of p53，and then increase HLFI-alpha role in expression of VEGF target molecules to influence angiogenesis. Thus, VEGF-target inhibiting of ovarian cancer blood vessels has been a new ideas for treatment of ovarian cancer. In our initial research we have confirmed that TCM compound(LCSSY) can Inhibit cancer cell proliferation，probably by down regulating expression of CTNNB1, HIF-1α and up - regulateing expression of FADD and PTEN and etc, Induced apoptosis in cancer cells, reducing cell adhesion.In order to confirm the mechanism of the TCM compound (LCSSY), we put the ovarian cancer cells SKOV3 and tissue as the research object, through the invitro and in vivo exeperiment, to explore how LCSSY regulate on expression of related proteins and gene in the signaling pathways, to clarify LCSSY mechanism of inhibition of ovarian tumor angiogenesis. At the same time through the optimal filtration of the LCSSY effective components, to provide a scientific basis and foundation support for traditional Chinese medicine treatment for ovarian cancer .

侵略性卵巢癌新生血管由内皮细胞萌芽，促进宿主血管新生因子（如VEGF）的释放引起癌细胞内皮活化。研究表明JAK/STAT信号通路中STAT3能直接调控VEGF的转录、抑制p53的表达，从而上调HLFI-α作用的VEGF靶分子的表达来影响血管生成。因此以VEGF为靶点抑制卵巢癌血管生成成为卵巢癌治疗的新思路。本课题组既往研究证实中药复方理冲生髓饮（LCSSY）能抑制卵巢癌细胞增殖，其机制与下调CTNNB1、HIF-1α及上调FADD 、PTEN等表达，诱导癌细胞凋亡、减少癌细胞黏附有关。为进一步明确LCSSY是否借助JAK/STAT通路影响VEGF的转录来抑制血管的生成，本课题从体内外水平以人卵巢癌细胞和组织为研究对象，探讨LCSSY对信号通路中相关蛋白和基因表达的调控，阐明LCSSY抑制卵巢肿瘤血管生成的作用机制，同时对LCSSY有效组分进行优化筛选，为中药治疗卵巢癌提供科学依据与基础支持

课题组已按年度计划基本完成课题任务。建立理冲生髓饮的指纹图谱和抗卵巢癌活性的评价方法，通过对其谱效相关性进行研究，确定理冲生髓饮的有效组分，确立其药效物质基础。从体外、体内两方面对理冲生髓饮有效组分进行抗卵巢癌血管生成实验研究，证实理冲生髓饮有效组分对卵巢癌血管生成有抑制作用，其作用机制与JAK/STAT信号通路有关，通过抑制JAK-STAT信号通路上JAK2、STAT3基因的表达降调节血管生成因子VEGF，影响卵巢癌血管生成。综上所述，本课题组从体内外水平以人卵巢癌细胞和组织为研究对象，探讨理冲生髓饮对JAK/STAT信号通路中相关蛋白和基因表达的调控，阐明理冲生髓饮对卵巢癌肿瘤血管生成的作用机制，同时对理冲生髓饮有效组分进行优化筛选，为中药治疗卵巢癌提供科学依据与基础支持。