摘要
目的观察索拉菲尼单药以及联合吉西他滨不同顺序给药对KRAS基因突变的非小细胞肺癌A549细胞的效应及其机制。方法索拉菲尼和吉西他滨单药以及不同序贯给药作用于A549细胞株。MTT法检测增殖抑制作用;流式细胞仪检测细胞周期变化;蛋白质印迹法检测p-ERK及Bcl-2的变化。结果索拉菲尼和吉西他滨作用于A549细胞72 h的IC50值分别为(5.91±0.22)μmol.L-1,(10.38±0.80)nmol.L-1;且先用吉西他滨后用索拉菲尼有明显的协同效应。索拉菲尼和吉西他滨分别将A549细胞阻滞于G0/G1期和S期;且先用吉西他滨后用索拉菲尼组的p-ERK及Bcl-2下降最明显。结论索拉菲尼能抑制A549细胞的生长,且先吉西他滨后索拉菲尼的序贯方式能产生明显的协同效应。
Objective To explore the efficacy and the mechanisms of sorafenib alone and in combination with gemcitabine on human non-small cell lung cancer A549 cells harboring KRAS mutations.Methods A549 cells were exposured to sorafenib alone and in combination with gemcitabine under three different sequence-dependent schedules.MTT assay was applied to assess the antiproliferative effects.The flow cytometry（FCM）was used to analyze the alteration of cell cycle.The change of p-ERK,and Bcl-2 level was measured by western blotting.Results At 72 h the IC50 values of sorafenib and gemcitabine for A549 cells were（5.91±0.22） μmol.L-1 and（10.38±0.80） nmol·L-1,respectively.The sequence of gemcitabine followed by sorafenib showed a significant synergic effect.Sorafenib resulted in cell cycle arrest at G0/G1 phase,while gemcitabine induced cell cycle arrest at S phase.The level of p-ERK and Bcl-2 reached its lowest level in A549 cells treated with gemcitabine followed by sorafenib.Conclusion Sorafenib can inhibit the growth of A549 cells.The sequence of gemcitabine followed by sorafenib can produce significant synergism.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2013年第3期196-198,共3页
The Chinese Journal of Clinical Pharmacology
基金
安徽省年度科研计划基金资助项目(09020303042
11070403061)
