斯诺普利抑制循环肿瘤细胞粘附于脐静脉内皮细胞的作用研究  

Effect of S-nitrosocaptopril on adhesion of circulating tumor cells to umbilical vein endothelial cells

作　　者：练殊 卢余盛 程云龙 谢瑞芝 李书慧 于婷[1] 梁海燕[1] 贾力[1] LIAN Shu;LU Yu-sheng;CHENG Yun-long;XIE Rui-zhi;LI Shu-hui;YU Ting;LIANG Hai-yan;JIA Lee(Cancer Metastasis Alert and Prevention Center,Fuzhou University,Fuzhou 350002,China)

机构地区：[1]福州大学肿瘤转移的预警和预防研究所,福州350002

出　　处：《药物分析杂志》2019年第1期133-140,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金面上项目(项目编号:81273548;2013-2016):一氧化氮在干预循环肿瘤细胞粘附于血管内膜的作用;国家自然科学基金(项目编号:81703555;2018-2020):基于一氧化氮通过改善血液微环境干预肿瘤血路转移的分子机制研究

摘　　要：目的:探索斯诺普利(Cap-NO)干预循环肿瘤细胞(CTCs)粘附于人脐静脉内皮细胞(HUVECs)的作用。方法:UV-Vis检测在不同时间点及不同浓度梯度下Cap-NO的特征吸收峰(300 nm)峰值;MTT法检测Cap-NO对HUVECs和HT-29的毒性;粘附实验检测Cap-NO抑制肿瘤细胞HT-29粘附到HUVECs的效率;流式检测Cap-NO对肿瘤细胞粘附分子及整合素活性的作用;qRT-PCR和三磷酸腺苷(ATP)检测Cap-NO对肿瘤细胞HK1、HK2、MMP2的mRNA表达和ATP水平。结果:Cap-NO的特征峰(300 nm)峰值,随着浓度的减小和时间的延长而减小;Cap-NO对2种细胞都表现为低毒性;Cap-NO可抑制肿瘤细胞粘附到人脐静脉内皮细胞,且与给药浓度成正比;对肿瘤细胞的分子CD44具有抑制作用,且与给药浓度成正比;Cap-NO也可抑制HK1、HK2、MMP2的mRNA表达并降低ATP的形成,抑制肿瘤能量代谢。结论:Cap-NO是一种有效的NO供体化合物,在低细胞毒性浓度范围内能有效干预肿瘤细胞粘附于血管内皮细胞,抑制肿瘤细胞能量代谢,可能具有预防肿瘤转移的作用。Objective:To explore the effect of Cap-NO on the adhesion of circulating tumor cells(CTCs) to human umbilical vein endothelial cells(HUVECs).Methods:UV-Vis was used to detect the characteristic absorption peak(300 nm)of Cap-NO at different time points and different concentration gradients.The cytotoxicity of Cap-NO to HUVECs and HT-29 cells was detected by MTT assay.Adhesion assay was used to detect the Cap-NO adhesion inhibition efficiency of HT-29 tumor cells to HUVECs.Flow cytometric analysis was used to detect the effect of Cap-NO on tumor cells adhesion molecules and integrin activity.q RT-PCR and ATP experiment were used to detect the expression of tumor cells mRNA of HK1,HK2 and MMP2 and adenosine triphosphate(ATP) levels.Results:The characteristic peak of Cap-NO(300 nm)decreased with the decrease of concentration and the prolongation time.Cap-NO showed low toxicity of HT-29 cells and HUVECs.Cap-NO inhibited the adhesion of tumor cells to HUVECs with the concentration of it.Cap-NO inhibited the growth of CD44,which was proportional to the concentration of drug.Cap-NO inhibited the mRNA expression of HK1,HK2 and MMP2 and reduced the formation of ATP to inhibit tumor energy metabolism.Conclusion:The present studies proved that Cap-NO is an effective NO donor compound.It can effectively interfere with the adherence of tumor cells to vascular endothelial cells and inhibit the energy metabolism of tumor cells in a low cytotoxic concentration range.It may have the effect of preventing metastasis of cancer.

关 键 词：一氧化氮 巯亚硝基卡托普利 肿瘤转移 抑制粘附 循环肿瘤细胞(CTCs) 三磷酸腺苷(ATP) 

分 类 号：R917[医药卫生—药物分析学]