摘要
目的:探讨Notch通路特异性阻断药物MRK-560在体外抑制原代培养脑胶质瘤细胞增殖及诱导肿瘤细胞凋亡的能力。方法:选取24例脑胶质瘤标本进行原代分离以获取脑胶质瘤细胞,分别给予不同浓度的MRK-560共培养48 h,检测肿瘤细胞胞内γ-secretase活性、肿瘤细胞的增殖能力及肿瘤细胞的凋亡水平。结果:5～40μg/mL MRK-560可抑制脑胶质瘤细胞γ-secretase活性和脑胶质瘤细胞的增殖(P<0.05)。MRK-560共培养组与空白对照组凋亡率分别为(47.6±19.2)%与(6.3±4.2)%,两组比较,差异有统计学意义(P<0.01)。加入MRK-560后,Notch通路重要的效应分子NICD蛋白的表达被明显抑制。结论:Notch受体阻断剂MRK-560具有良好的体外抗肿瘤活性,在治疗脑胶质瘤方面具有非常重要的应用前景。
Objective ：To investigate the effects of MRK-560, a Notch signaling pathway specific inhibitor, on suppression of primary glioma cell proliferation and induction in vitro. Methods： The 24 glioma specimens were obtained for collection of cerebral glioma cells, which were subjected to primary culture with MRK-560 at different concentrations for 48 hours. The γ-seeretase activity, glioma cell proliferation and apoptosis were assayed. Results： MRK-560 at 5-40μg/mL inhibited the γ-secretase activity and glioma cell proliferation （both P 〈 0.05 ）. Following co-culture with MRK-560, the apoptosis of glioma cells was substantially potentiated when compared with normal controls （ [ 47.6 ± 19.2 ] % vs. [ 6.3 ± 4. 2 ] %, P 〈 0.01 ）. The addition of MRK-560 resuhed in marked attenuation of expression of N1CD, the selective effectors of Notch signaling pathway. Conclusion： MRK-560, a Notch signaling pathway inhibitor, is featured by potent anti-glioma effects in vitro and merits further studies for the treatment of cerebral glioma.
出处
《广州医学院学报》
2012年第6期18-21,共4页
Academic Journal of Guangzhou Medical College
