坎地沙坦对子宫内膜癌血管生成的影响

目的：探讨血管紧张素Ⅱ-1型受体（Angiotensin Ⅱ type 1 receptor,AT1R）拮抗剂坎地沙坦是否通过抑制肿瘤血管生成而抑制子宫内膜腺癌裸鼠荷瘤模型肿瘤生长.方法：将24只BALB/C裸鼠随机分成3组,建立子宫内膜癌裸鼠荷瘤模型,分为对照组、坎地沙坦10mg·kg-1·d-1组,坎地沙坦100mg·kg-1·d-1组.观察各组裸鼠成瘤时间、测量肿瘤体积、绘制成瘤曲线并计算抑瘤率.免疫组化法检测皮下移植瘤血管内皮生长因子（vascular endothelial growth factor,VEGF）和微血管密度（microvascular density,MVD）的不同.结果：与对照组相比,两组坎地沙坦组皮下移植瘤体积均显著减少（P＜0.05）,并且两组坎地沙坦组皮下移植瘤VEGF、MVD的表达明显降低（P＜0.05）.结论：AT1R拮抗剂坎地沙坦可以抑制肿瘤的血管生成,从而抑制子宫内膜癌的生长,故AT1R拮抗剂将可能成为治疗子宫内膜癌的一种新型药物.

Effects of candesartan on angiogenesisin in a mouse model of endometrial carcinomatosis

Objective：To determine whether AT1R blocker candesartan could inhibit endometrial cancer progression and angiogenesis in vivo.We used Ishikawa-transplanted （ip） nude mice as a model of endometrial carcinoma.Methods：All 24 BALB/C nude mice were randomly divided into three groups with 8 mice each group and established mice models of endometrial carcinoma.The first group was established as control one,in contrast,the second group was treated by candesartan 10mg · kg-1 · d-1 and the third group was given candesartan 100mg · kg-1 · d-1.From the 1st day of the transplantion,the control group was administrated by 0.2ml normal saline （ip） for 28 days while the 2nd group was given candesartan 10mg/kg with 0.2ml normal saline （ip） per day for 28 days,the 3rd group was treated by candesartan 100mg/kg with 0.2ml normal saline（ip） per day for 28 days.Tumors planted on subcutaneous tissue were resected from each mouse histologically and immunohistochemically analyzed.The time of tumorigenesis,tumor formation rates and the tumor volumes were observed.To compose the tumor-growth curves,measured the weight changes of the nude mice,and computed the tumorgenesis inhibition rates.We took the immunohistochemical method to observe the effects of candesartan in expression of vascular endothelial growth factor （VEGF） and microvascular density （MVD） from mice xenograft models.Results：Though compared with control group administration （ip） of candesartan at a dose of 10 and 100mg · kg-1 · d-1 for 28 days resulted in a marked reduction of tumors volume （P ＜ 0.05）,there were no significant differences between 10 and 100mg · kg-1 · d-1 candesartan groups （P ＞0.05）.VEGF,CD34 expressions in mice models of endometrial carcinoma in 10mg · kg-1 · d-1 and 100mg · kg-1 ·d-1 candesartan-treated groups were significantly reduced compared with those in the control group （P ＜ 0.05）.Conclusion：Administration of candesartan into mice models of endometrial carcinoma resulted in the reduction of tumor volumes by suppressing tumor angiogenesis,therefore,AT1R blockade therapy may become a novel strategy for endometrial carcinoma treatment.