一氧化氮释放型阿司匹林对荷瘤小鼠前列腺癌血管形成的抑制作用

Inhibitory effect of nitric oxide-donating aspirin against prostatic cancer angiogenesis in tumor-bearing mice

目的探讨一氧化氮释放型阿司匹林(NO-ASA)对小鼠皮下种植前列腺癌的生长及肿瘤血管形成的抑制作用。方法皮下荷前列腺癌小鼠体内注射NO-ASA后监测肿瘤生长情况;处死小鼠后以ELISA法检测小鼠血清VEGF的表达,实时定量PCR法检测肿瘤中VEGF mRNA的表达,免疫组化法检测肿瘤中CD34的表达并量化微血管数目,以未注射NO-ASA的皮下荷前列腺癌小鼠为对照。受精鸡胚尿囊膜(HET-CAM)试验检测NO-ASA在体外对血管形成的影响。结果小鼠体内注射NO-ASA后皮下种植的前列腺癌的生长受到抑制,小鼠血清以及肿瘤组织的VEGF表达明显降低,肿瘤组织中的CD34表达减少,与对照组相比差异有统计学意义(P<0.05,P<0.01)。NO-ASA对受精鸡卵尿囊膜上的血管生长也有明显抑制作用。结论 NO-ASA可抑制前列腺癌肿瘤生长和血管形成。

Objective To study the inhibitory effect of nitric oxide-donating aspirin（NO-ASA） on prostatic cancer growth and angiogenesis in subcutaneously-injected tumor in mice.Methods The tumor-bearing mice were subcutaneously injected with NO-ASA,and the tumor growth was observed.ELISA was used to assay the expression of VEGF in mouse sera;real-time PCR was used to examine the expression of VEGF mRNA in tumor tissues;immunohistochemistry was used to detect CD34 expression and to quantify the number of microvessels in the tumor;and Hen＇s egg test chorioallantoic membrane （HET-CAM） was employed to detect the in vitro angiogenesis.Results NO-ASA inhibited the prostate cancer growth in mice.The expression of VEGF was greatly decreased in the serum and tumor tissues,and CD34 expression was significantly decreased in the tumor tissues compared with the control group （P〈0.05,P〈0.01）.NO-ASA also greatly inhibited the angiogenesis in HET-CAM.Conclusion NO-ASA can inhibit prostate cancer growth and angiogenesis.