摘要
目的:研究哌立福辛对雷帕霉素耐药的非小细胞肺癌细胞株生长的抑制作用和机制。方法:用SRB法检测哌立福辛单用以及联用LiCl对细胞株生长的抑制作用。用Western blotting法检测哌立福辛对细胞内Akt,GSK3β信号的调控作用。结果:哌立福辛对雷帕霉素敏感和耐药细胞株的生长有相似的抑制作用。在耐药细胞上,哌立福辛未明显抑制Akt的磷酸化,却可以显著抑制GSK3β的磷酸化,从而激活GSK3β。用LiCl抑制GSK3β的活性可以阻断哌立福辛对耐药细胞生长的抑制作用。结论:哌立福辛可以通过激活GSK3β抑制雷帕霉素耐药的非小细胞肺癌细胞的生长。
AIM： To investigate the effects and mechanisms of perifosine on the growth of rapamcyin resistant NSCLC cells. METHODS： The growth inhibitory effects of perfisoine with or without LiCl on NSCLC cells were detected by SRB assay.The regulatory effects of perifosine on Akt,GSK3β singaling were detected by Western blotting.RESULTS：Perifosine had similar inhibitory effects on the growth of rapamycin resistant and sensitive cells.Perifosine inhibited phosphorylation of GSK3β without significant alteration of Akt phosphorylation,and thus activated GSK3β in rapamycin resistant cells.The inhibitor of GSK3β-LiCl blocked perifosine＇s inhibitory effects on the growth of rapamycin resistant cells.CONCLUSION： Perifosine inhibits growth of rapamycin resistant NSCLC cells through activating GSK3β.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2011年第4期389-393,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金(30873099)
教育部科学技术研究重点项目(209050)
南京医科大学引进人才科研启动基金(10RC01)
