干扰素α对U937細胞促凋亡及抗增殖作用及其机制.docVIP

干扰素α对U937細胞促凋亡及抗增殖作用及其机制 　【摘要】 为了研究干扰素α对白血病细胞U937細胞的抗增殖作用及其机制，用不同浓度的干扰素α(500 U/L、1 000 U/L、2 000 U/L、3 000 U/L、4 000 U/L) 对U937細胞作用不同时间（0、12、24、36 和48小时）, 用MTT法检测细胞生长抑制率，应用流式细胞术（FCM）检测细胞凋亡率，RTPCR方法分析cyclin E mRNA的表达。结果表明：不同浓度的干扰素α处理细胞后，U937细胞生长明显受抑， 2 000 U/L干扰素α能引起细胞凋亡，凋亡率为25.28%-70.54%（Plt;0.01），细胞周期相关基因cyclin E mRNA表达降低；干扰素α对U937细胞的抑制率,呈浓度时间依赖性。结论： 干扰素α对U937细胞有明显抗增殖和促凋亡作用，此结果将为干扰素α在白血病临床治疗方面的应用提供有力的实验证据。 【关键词】 干扰素α U937细胞 白血病 Apoptosisinducing and Antiproliferation Effect of Interferonα on U937 Cells and Its Mechanism Abstract This study was aimed to investigate the antiproliferation effect of interferonα(IFNα) on leukemic U937 cells and its mechanism．The U937 cells were given with various concentrations of IFNα(500, 1 000, 2 000, 3 000 and 4 000 U/L) and at different time (0, 12, 24, 36, 48 hours), the inhibitory ratio was measured by MTT assay, apoptosis rate was detected by flow cytometry(FCM), the expression of cell cycleassociated cyclin E mRNA was measured by RTPCR. The results showed that IFNα (2 000 U/L) could cause apoptosis, after being treated by various concentrations of IFNα, the growth of U937 cells was inhibited significantly, the apoptosis rate was 25.82%-70.54% (Plt;0.01), the cycleassociated cyclin E mRNA expression decreased, the growth of U937 cells was significantly inhibited, the suppression of U937 by IFNα was both in timeand dosedependent manner．It is concluded that IFNα has apparent antiproliferation and apoptosisinducing effects on U937 cells. These results will provide strong laboratory evidence for IFNα clinical application in leukemia therapy. Key words interferonα；U937 cell；leukemia 干扰素α是目前用于临床治疗最重要的细胞因子之一。它具有广泛多变的生物学作用，诸如免疫调节、抗感染、抗病毒作用，尤其是对病毒性肝炎具有良好的治疗作用［1］。最新研究表明，干扰素α是一种非常有效的抗肿瘤细胞因子，并且对许多恶性疾病，例如肺癌、慢性粒细胞白血病均有显著效果［2］。干扰素α虽然已经广泛用于各种恶性肿瘤，但其抗肿瘤机制还不清楚。干扰素α可能间接地通过调节免疫调制和抗血管生长反应或直接通过影响肿瘤细胞的增殖和细胞分化来介导抗肿瘤作用。干扰素α的直接和间接作用都是由干扰素刺激基因（IFNtimulated gene, ISG)亚群诱导引起的。除此之外，还有ISGS还具有致凋亡作用［3，4］。 为了阐明干扰素α的抗白血病机制，我们研究了从5