重组人血管内皮抑素体外抗多发性骨髓瘤的初步研究

本研究旨在探索重组人血管内皮抑素（recombinant human endostatin，rhES）体外对多发性骨髓瘤（MM）细胞生长的抑制作用及其机制。采用台盼蓝拒染法、MTT法检测rhES对MM细胞的增殖抑制作用，用透射电子显微镜及Annexin V—PI双标记流式细胞术检测rhES对MM细胞的凋亡诱导作用。结果表明：rhES在体外浓度为50、100和200μg／ml时，与多发性骨髓瘤细胞株CZ-1细胞作用72小时，抑制率分别为10．5％、17．9％和23．5％，其抑制CZ-1细胞增殖作用呈浓度及时间依赖性；rhES体外浓度为0—400μg／ml时对正常人骨髓单个核细胞的生长活性无明显抑制作用；而体外浓度为50—200μg／ml时rhES对多发性骨髓瘤原代细胞生长活性有抑制的作用，并且其抑制作用呈浓度及时间依赖性。rhES在体外浓度为100μg/ml时，与CZ-1细胞作用72小时，在透射电子显微镜检测可见典型的细胞凋亡的表现，流式细胞术检测其凋亡率为21．37％。结论：rhEs在体外有抑制多发性骨髓瘤细胞生长的作用，其作用机制是诱导细胞凋亡。rhES可能是用于治疗多发性骨髓瘤的潜在药物。

Antimyeloma Effect of Recombinant Human Endostatin In Vitro

The aim of this study was to investigate the antimyeloma effect of recombinant human endostatin （rhES） in vitro and its mechanism. The inhibitory effect of rhES on proliferation of multiple myeloma cell line CZ-1 was assayed by trypan blue dye exclusion and MTT method, the apoptosis-inducing effect of rhES on CZ-1 cells was detected by transmission electron microscopy and flow cytometry with Annexin V-FITC and PI double staining. The effects of rhES on primary bone marrow cells of patients with/VIM and healthy adults were also investigated. The results showed that the rhES at concentrations of 50, 100 and 200 μg/ml for 72 hours could inhibit the proliferation of CZ-1 cells, and their inhibition rates were 10.5%, 17.9% and 23.5% respectively. The inhibitory effect of rhES on CZ-1 cells was time- and dose-dependent. 50 - 200 μg/ml rhES could also inhibit the growth of primary bone marrow cells of multiple myeloma patients, while 0 -400 μg/ml rhES had no inhibitory effect on primary bone marrow cell of healthy adults. 100 μg/ml rhES could induce CZ-1 cell apoptosis after administration for 72 hours. The typical manifestation of apoptotic cells could be observed by transmission electron microscopy. The apoptotic rate of CZ-1 cells was 21.37%. It is concluded that rhES can inhibit the proliferation of multiple myeloma cells by inducing apoptosis. Whether rhES may be a candidate medicine for the treatment of multiple myeloma is to be further studied.