选择性COX-2抑制剂Celecoxib诱导胶质瘤细胞凋亡作用机制初探

Primary Mechanism of Selective COX-2 Inhibitor Celecoxib Induce C6 Glioma Cells Apoptosis in vitro

背景与目的:选择性COX-2抑制剂具有诱导多种肿瘤细胞凋亡的作用,但在胶质瘤方面研究还不多见,本研究目的是探讨选择性COX-2抑制剂塞来昔布(Celecoxib)诱导胶质瘤C6细胞凋亡,及其在诱导胶质瘤细胞凋亡中的作用机制。方法:应用PGE2检测、吖啶橙染色、流式细胞仪(FCM)检测不同浓度的Celecoxib对胶质瘤C6细胞作用,通过放免法检测不同浓度Celecoxib作用于胶质瘤C6细胞后PGE2的含量,通过吖啶橙染色从形态上观察治疗组细胞的形态学变化,流式细胞仪检测各组细胞发生凋亡的情况。结果:随Celecoxib浓度增加而PGE2合成减少(P>0.05),吖啶橙染色荧光染色对照组细胞核DNA为均匀黄色或黄绿色的荧光,治疗组(Celecoxib50μmol/L)凋亡细胞的细胞核或细胞质内可见致密浓染的黄绿色荧光或黄绿色碎片,Celecoxib浓度为12.5μmol/L和50μmol/L时,FCM法检测凋亡分别为5.83%和15.32%,Celecoxib对C6胶质瘤细胞增殖抑制作用具有浓度依赖性,细胞凋亡随浓度增加而增多。结论:Celecoxib具有诱导胶质瘤C6细胞凋亡的作用并呈剂量依赖性,随PGE2合成下降细胞凋亡增多,PGE2途径是Celecoxib诱导胶质瘤细胞凋亡机制之一,对胶质瘤的治疗有重要意义。

BACKGROUND ＆ OBJECTIVE： To investigate celecoxib＇s function of inducing C6 glioma cells apoptosis in vitro. METHODS： Cell apoptosis was evaluated by PGE2, acridine orange （AO） stain and flow cytometry（FCM） with different concentration of celecoxib. RESULTS： Apoptosis of C6 glioma cells in treatment group can be seen with AO stain; FCM detected 15.32% and 5.83% apoptosis rate, at different celecoxib concentration of 50μmol/L and 12.5μmol/L, respectively. There was a dose-dependent apoptosis of cell by celecoxib. PGE2 decreased in high dose celecoxib （P〈 0.05）. Celeeoxib could increase apoptosis in vitro. CONCLUSION： Celecoxib could induce apoptosis of C6 glioma cells, and PGE2 played an important rule in this course.