CAJ | 학술논문

目的探讨I型γ-分泌酶抑制剂(GSI-I)对U87、U251胶质瘤细胞的增殖抑制及诱导凋亡作用.方法应用GSI-I作用于U87、U251胶质瘤细胞,通过MTT法观察GSI-I对上述两种细胞的增殖抑制作用,通过流式细胞仪检测GSI-I对该两种细胞细胞周期的影响及诱导凋亡的作用.结果RT-PCR及实时定量荧光RT-PCR结果显示,GSI-T可明显抑制胶质瘤细胞中Notch通路的活性,主要体现为Notch通路的靶基因Hes-1表达明显下调.MTT检测结果显示2.5μmol/L及以上浓度的GSI-I对U87及U251胶质瘤细胞有明显的增殖抑制作用.与对照组比较,差异有统计学意义(P<0.05),且该抑制作用呈剂量依赖型增加.流式细胞检测结果显示GSI-I主要使U87胶质瘤细胞的细胞周期阻滞在G1期而抑制细胞增殖,对于U251胶质瘤细胞则主要通过诱导凋亡来抑制增殖.结论 GSI-I可明显抑制U87及U251胶质瘤细胞的增殖并诱导凋亡,为恶性胶质瘤的临床治疗提供了理论参考依据.
목적 탐토I형γ-분비매억제제(GSI-I)대U87、U251효질류세포적증식억제급유도조망작용.방법 응용GSI-I작용우U87、U251효질류세포,통과MTT법관찰GSI-I대상술량충세포적증식억제작용,통과류식세포의검측GSI-I대해량충세포세포주기적영향급유도조망적작용.결과RT-PCR급실시정량형광RT-PCR결과현시,GSI-T가명현억제효질류세포중Notch통로적활성,주요체현위Notch통로적파기인Hes-1표체명현하조.MTT검측결과현시2.5μmol/L급이상농도적GSI-I대U87급U251효질류세포유명현적증식억제작용.여대조조비교,차이유통계학의의(P<0.05),차해억제작용정제량의뢰형증가.류식세포검측결과현시GSI-I주요사U87효질류세포적세포주기조체재G1기이억제세포증식,대우U251효질류세포칙주요통과유도조망래억제증식.결론 GSI-I가명현억제U87급U251효질류세포적증식병유도조망,위악성효질류적림상치료제공료이론삼고의거.
Objective To investigate the role of gamma secretase inhibitor-I (GSI-I) in cell proliferation and apoptosis of human glioma cell lines U87 and U251.Methods RT-PCR and fluorescent quantitative RT-PCR (qRT-PCR) were employed to evaluate the expressions of Notch receptors and their target gene Hes-I in both U87 and U251 cells treated by GSI-I,respectively.Then,MTT assay was used to examine the effects of GSI-I on cell proliferation of the 2 glioma cells.Meanwhile,flow cytometry technique was also employed to detect the cell cycle changes and apoptosis induced by GSI-I treatment.Results The activity of Notch pathway was inhibited by GSI-I treatment through down-regulating the expression of Notch receptors target gene Hes-I in both U87 and U251 cells.Treatment with 2.5μmol/L GSI-I or above concentrations could significantly induce the cell cycle arrest of U87 and U251 cells and these effects were positively concentration-dependent.Flow cytometry technique showed that GSI-I inhibited the cell proliferation by inducing the cell cycle arrest of U87 cells at GI phase and inducing the apoptosis of U251 cells.Conclusion GSI-I can dramatically inhibit the cell proliferation and induce the apoptosis of U87 and U251 cells,providing a reliable evidence for clinical glioma treatment.