重组人血管内皮抑素对多发性骨髓瘤血管新生的影响  

Effect of human recombinant endostatin on the angiogenesis induced by multiple myeloma cell line in vitro through endothelial cells

作　　者：王信峰[1] 朱婧[1] 黄红铭[1] 薛英姿[1] 丁润生[1] 李晓红[2] 

机构地区：[1]南通大学附属医院血液科,江苏南通226001 [2]南通大学附属医院外科综合实验室,江苏南通226001

出　　处：《苏州大学学报（医学版）》2012年第1期45-49,共5页Suzhou University Journal of Medical Science

基　　金：南通市科技项目(S2009026)

摘　　要：目的观察重组人血管内皮抑素注射液对人脐静脉内皮细胞株(HUVEC)和多发性骨髓瘤细胞株KM3增殖、凋亡及共培养体系中血管生成的影响。方法观察不同浓度的内皮抑素对HUVEC和KM3细胞株的增殖抑制作用;检测有效浓度的内皮抑素对HUVEC和KM3细胞株的凋亡作用;建立HUVEC和KM3的隔离共培养和混合共培养体系,检测共培养体系中不同浓度的内皮抑素作用后对于HUVEC血管生成的影响;检测经内皮抑素作用后对混合共培养、隔离共培养上清中VEGF浓度的影响。结果不同浓度的内皮抑素持续作用72 h,对HUVEC具有抑制增殖作用,且在50-200 ng/ml的剂量范围内呈现浓度依赖关系,而对KM3细胞未见明显作用;有效浓度的内皮抑素(100、200 ng/ml)可诱导HUVEC凋亡,而对KM3未见明显作用;共培养体系中,内皮抑素可抑制HUVEC的管状结构形成;经不同浓度内皮抑素作用后,细胞培养上清中VEGF的分泌量减少。结论内皮抑素能抑制HU-VEC的增殖;诱导HUVEC的凋亡;通过血管内皮抑制骨髓瘤细胞的促血管新生作用;抑制VEGF的分泌可能是其作用机制之一。Objective To observe effect of human recombinant endostatin（ES） in proliferation,apoptosis of human umbilical vein endothelial cells（HUVEC） and myeloma KM3 cells,and angiogenesis inhibition in HUVEC-KM3 co-culture system.Methods Cell proliferation in different concentration of ES was determined.Annexin V-FITC assay was applied to detect the changes of apoptotic cells.The co-culture system of KM3 cells and HUVEC was treated with ES at various concentrations,and the tubule formation assay was applied.The expression levels of VEGF in cell supernatant were detected by ELISA.Results The proliferation inhibited effect in HUVEC of ES was observed,and the inhibited effect was dose-dependent from 50ng/ml to 200ng/ml.ES（100,200ng/ml） also induced apoptosis of HUVEC cells.However,our results showed that ES was ineffective on the inhibition and apoptosis of KM3 cells.In the co-culture systems,the areas of the capillary-like structures decreased while the concentration of ES increased.The inhibition of VEGF secretion in KM3 cells is dose-dependent.Conclusion ES can inhibit the proliferation and induce apoptosis of HUVEC cells.ES can significantly inhibit angiogenesis ability of myeloma through vascular endothelial cells.Inhibition of VEGF secretion may be one of the mechanisms of its pharmacological effects.

关 键 词：人重组内皮抑素 多发性骨髓瘤 血管新生 共培养 血管内皮生长因子 

分 类 号：R392.12[医药卫生—免疫学]