论文部分内容阅读
目的:研究雌激素受体部分拮抗剂α-双炔失碳酯(α-Ano)对体内、外肿瘤血管生成的抑制作用.方法:在C57BL/6小鼠中观察Lewis肺癌的生长情况,用免疫组织化学方法观察肿瘤微血管密度(MVD):在鸡胚绒毛膜尿囊膜(CAM)模型上观察药物对血管生成的影响;用台盼蓝排染法研究药物对人脐静脉内皮细胞(HUVEC)生长的作用;在体外观察了药物对HUVEC的由伤口引起的迁移和对胶原基质的粘附活性的影响;用荧光法间接测定一氧化氮(NO)水平.结果:α-Ano显著地抑制Lewis肺癌的MVD,同时抑制小鼠皮下接种的肿瘤生长,MVD的降低程度与肿瘤生长的抑制程度相关.α-ANO在CAM模型上也显示出对血管生成的抑制活性,抑制率达53％,17α-雌二醇对α-Ano抑制CAM血管生成的活性无明显拮抗作用;α-Ano对HUVEC的增殖和迁移活性有抑制作用,但对HUVEC对Ⅰ型胶原的粘附能力无明显影响.同时,α-Ano能够抑制HUVEC释放NO的水平,且具有时间和剂量依赖性.结论:α-Ano具有血管生成抑制活性,此作用是通过减少NO的释放,随后抑制内皮细胞的增殖和迁移而实现的.
OBJECTIVE: To study the inhibitory effect of α-Ano, a partial antagonist of estrogen receptor, on tumor angiogenesis in vivo and in vitro.Methods: The growth of Lewis lung carcinoma was observed in C57BL / 6 mice with Immunohistochemistry was used to observe the microvessel density (MVD). The effects of drugs on angiogenesis were observed in chick embryo chorioallantoic membrane (CAM) model. The effect of drugs on human umbilical vein endothelial cells (HUVECs) ) Were observed in vitro.It was observed in vitro that the drug induced wound migration and the adhesion activity to collagen matrix of HUVEC.The level of nitric oxide (NO) was measured indirectly by fluorescence method.Results: α-Ano significantly inhibited Lewis lung cancer MVD, while inhibiting subcutaneous tumor growth in mice, the reduction of MVD and the degree of inhibition of tumor growth.α-ANO in CAM model also showed inhibition of angiogenesis, the inhibition rate of 53% 17α-estradiol had no obvious antagonism on the activity of α-Ano inhibiting CAM angiogenesis; α-Ano inhibited the proliferation and migration of HUVEC, but had no obvious effect on the adhesion ability of HUVEC to type Ⅰ collagen. , α-Ano can inhibit the release of HUVEC NO In a dose-and time-dependent manner.Conclusion: α-Ano has an angiogenic inhibitory activity by reducing the release of NO and subsequently inhibiting the proliferation and migration of endothelial cells.