论文部分内容阅读
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 ability of MRK-560, a specific blocker of Notch pathway, to inhibit the proliferation of primary cultured glioma cells and induce tumor cell apoptosis in vitro. Methods: Twenty-four glioma samples were selected for primary isolation to obtain glioma cells. The cells were co-cultured with different concentrations of MRK-560 for 48 h. The intracellular γ-secretase activity and the proliferation of tumor cells And the level of apoptosis of tumor cells. Results: MRK-560 at 5 ~ 40μg / mL inhibited the activity of γ-secretase and the proliferation of glioma cells (P <0.05). The apoptosis rates of MRK-560 co-culture group and blank control group were (47.6 ± 19.2)% and (6.3 ± 4.2)%, respectively. There was significant difference between the two groups (P <0.01). After addition of MRK-560, the expression of NICD, an important effector of Notch pathway, was significantly inhibited. Conclusion: Notch receptor antagonist MRK-560 has good antitumor activity in vitro and has a very important application prospect in the treatment of gliomas.