摘要
目的 探讨全反式维甲酸 (ATRA)抑制视网膜母细胞瘤 (Rb)细胞生长并诱导其凋亡的作用及信号转导机制。方法 应用3 H 胸腺嘧啶掺入分析法观察ATRA对细胞生长的抑制作用 ;用流式细胞仪分析ATRA对Y79细胞周期的影响 ;以DNA片段凝胶电泳分析细胞凋亡 ;用Westernblot分析c jun氨基末端激酶 (JNK)的磷酸化。结果 ATRA可明显抑制Y79细胞的生长 ,1μmol/L处理 36h时 ,3 H 胸腺嘧啶掺入率下降达 4 0 % ,Y79细胞被阻滞于G0 /G1期 ,并出现Sub G1峰。ATRA可诱导Y79细胞凋亡 ,此凋亡过程可被JNK的阻断剂Curcumin阻断 ;在此过程中 ,JNK被激活并磷酸化。结论ATRA可抑制Y79细胞生长并诱导其凋亡 ,其过程是由磷酸化的JNK介导 ,提示ATRA可能是一种潜在的抗Rb化疗药物。
Objective To investigate the mechanism of all trans retinoid acid (ATRA) inhibition of cell growth and induction of apoptosis in human retinoblastoma Y79 cells. Methods Antiproliferating effects of ATRA on Y79 cells were studied by 3 H thymidine incorporation. Cell cycle analysis was performed by flow cytometry, apoptosis of the ATRA treated cells was determined by DNA fragmentation analysis and JNK phosphorylation analyzed by Western blot. Results After 36h treatment of 1 μmol/L ATRA, 3 H thymidine incorporation decreased to 40% with Y79 cells arrested in G 0/G 1 and Sub G 1 peak appeared. DNA ladder was observed in DNA fragmantation analysis after 36h treatment of ATRA. Curcumin, a JNK blocker, blocked the apoptosis and the growth inhibition induced by ATRA. JNK was phosphorylated in 10 to 20 min. Conclusion ATRA can induce the apoptosis in Y79 cells by posphorylation of JNK, which suggests that ATRA may have clinical application prospects for treatment of retinoblastoma.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2003年第2期130-133,共4页
Chinese Journal of Oncology
