苯丁酸钠联合吉非替尼增强抑制NB4细胞的PKC信号传导途径  

Inhibitory effect of sodium phenylbutyrate combined with gefitinib on PKC of NB4 cells

作　　者：王旭[1] 李薇[1] 王冠军[1] 

机构地区：[1]吉林大学第一医院血液肿瘤科,吉林长春130021

出　　处：《吉林大学学报（医学版）》2007年第2期290-292,313,共4页Journal of Jilin University：Medicine Edition

基　　金：吉林省计划委员会资助课题(20031268)

摘　　要：目的:探讨联合应用苯丁酸钠(SPB)与吉非替尼对NB4细胞的抑制效果。方法:将NB4细胞随机分为对照组、PKC激动剂PMA组、PKC抑制剂H-7组、SPB组、SPB+PMA组、吉非替尼组、吉非替尼+PMA组及SPB+吉非替尼组。应用MTT法检测药物对细胞的抑制率,流式细胞仪检测细胞的凋亡情况,Western blotting法检测蛋白激酶C(PKC)、周期素依赖性激酶4(CDK4)及野生型P53蛋白的表达。结果:SPB+吉非替尼联合用药物组肿瘤细胞受到明显抑制,生长抑制率和增殖指数分别为92.80%和5.96%;与SPB组(生长抑制率和增殖指数分别为45.1%和29.6%)以及吉非替尼组(生长抑制率和增殖指数分别为61.0%和35.9%)相比,差异均有显著性(P<0.05);SPB+吉非替尼组P53表达增加,CDK4和磷酸化的PKC表达下降,与单纯用药组比较,差异均具有显著性(P<0.05)。结论:SPB与吉非替尼联合用药比单一用药明显提高肿瘤细胞的抑制率和促凋亡率,其机制是通过联合抑制PKC的信号传导通路从而阻滞肿瘤细胞的增殖周期。Objective To investigate the inhibitory effect of sodium phenylbutyrate （SPB） combined with gefitinib on NB4 cells. Methods The NB4 cells were divided into 8 groups randomly： control group, PMA group, H-7 group, SPB＋PMA group, gefitinib group, gefitinib＋PMA group, SPB＋gefitinib group. The inhibitory rate of medicine was detected by MTT, the apoptosis of NB4 cells was detected by flow cytometry, the expressions of PKC, CDK, and P53 were detected with Western blotting method. Results The NB4 cells were suppressed obviously. The rate of growth inhibition and proliferation index in SPB＋gefitinib group were 92.8% and 5.96%, those in SPB group were 45.1% and 29.6%, and gefitinib group were 61.0% and 35.9%, the differences were significant （P〈0.05）. The expression of P53 in SPB＋gefitinib group increased but CDK4 and p-PKC decreased, compared with curement only, the difference was significant （P〈0.05）. Conclusion SPB combined with gefitinib can significantly increase the apoptotic rate and inhibitory rate of tumor cells than SPB or gefitinib only, its mechanism is suppressing PKC to block the cell cycle.

关 键 词：苯丁酸钠 吉非替尼 药物疗法 联合 NB4细胞 蛋白激酶C 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]