米非司酮诱导子宫内膜癌组织血管内皮细胞凋亡

Mifepristone induces vascular endothelial cell apoptosis in endometrial carcinoma

目的 :探讨米非司酮治疗子宫内膜癌的作用机理。方法 :2 3例经诊断性刮宫、病理学检查确诊的子宫内膜癌患者 ,口服米非司酮 10 0mg d ,3～ 5d ,停药后次日行手术治疗。用原位末端标记法 (TUNEL)、SP法检测米非司酮对细胞凋亡、血管形成的影响。结果 :服用米非司酮前后子宫内膜癌细胞凋亡率无明显变化 ;服用米非司酮后出现血管内皮细胞凋亡 ,凋亡率为 2 .10 1± 1.6 6 3,P <0 .0 0 0 1。用药后子宫内膜癌组织血管内皮细胞生长因子 (vascularendothelialgrowthfactor ,VEGF)由 1.4 76± 0 .6 79降至 0 .5 6 3± 0 .5 12 ,P <0 .0 0 0 1;微血管密度 (microvesseldensity ,MVD)由 30 .6 7± 8.0 84降至 18.74± 5 .76 3,P <0 .0 0 0 1;用米非司酮后VEGF、MVD值的下降均与血管内皮细胞凋亡呈正相关。结论 :米非司酮通过下调VEGF ,诱导子宫内膜癌组织血管内皮细胞凋亡 ,抑制子宫内膜癌血管生成 ,提示米非司酮可能在抑制子宫内膜癌生长、转移方面发挥重要作用。

Objective:To investigate the mechanism and action of mifepristone in endometrial carcinoma.Methods:Pre and posttreatment endometrial tissue samples from 23 women with endometrial carcinoma were measured for changes in apoptotic activity and angiogenesis related to the administration of mifepristone. Apoptotic activity was detected using DNA in situ terminal deoxynucleotidyl transferas(TDT) mediated deoxyuridine triphosphate(dUTP) biotin nick ending labeling(TUNEL) assay. Vascular endothelial growth factor(VEGF) and microvessel density(MVD) of the tumors were assessed using immunohistochemistry for VEGF and CD34 antigen.Results:Apoptotic cells of tumor assay showed no statistical difference between pre and posttreatment endometrial carcinoma samples. Interestingly, endothelial cells apoptosis of microvessl in endometrial carcinomas arose after mifepristone therapy, apoptosis index(AI)of endothelial cells was 2.101±1.663,P<0.0001. VEGF and MVD significantly decreased in posttreatment carcinoma tissue. The decrease of VEGF and endothelial cells apoptosis showed a positive liner correlation. So did MVD and endothelial cells apoptosis.Conclusion:Mifepristone can induce microvascular endothelial cells apoptosis by downregulating VEGF and inhibit angiogenesis in endometrial carcinoma. These datum suggested that mifepristone might have important effects on inhibiting growth and metastasis of endometrial carcinoma.