BI2536对顺铂耐药的非小细胞肺癌细胞增殖的影响及机制  

Effects and mechanism of BI2536 on proliferation of cisplatin-resistant NSCLC cells

作　　者：李峰[1] 周玉冰[1] 韩超[1] 安琪[1] 李朵璐[1] 阚全程[1] 段震峰[1,2] 

机构地区：[1]郑州大学第一附属医院临床药学实验室,河南郑州450052 [2]美国哈佛大学麻省总医院癌症研究中心

出　　处：《中国医院药学杂志》2014年第16期1362-1365,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金面上项目(编号:81372875)

摘　　要：目的:观察BI2536在体外对顺铂敏感及耐药的非小细胞肺癌细胞增殖的影响。方法:用不同浓度的BI2536处理人非小细胞肺癌细胞A549和顺铂耐药的非小细胞肺癌细胞A549/DDP48 h后,采用MTT法测定BI2536对细胞增殖活性的影响,应用流式细胞术检测细胞凋亡的变化,Western blot法检测PLK1及PARP蛋白的表达水平的变化。结果:BI2536对A549/DDP增殖的抑制作用显著大于其对A549增殖的抑制作用,其IC50值分别为(9.9±0.4)nmol·L-1和(25.9±1.0)nmol·L-1(P<0.01)。BI2536处理48 h后流式细胞仪检测A549/DDP的凋亡率显著高于A549细胞(60.6%vs 20.3%,P<0.01)。Western blot法检测可见随BI2536浓度升高PLK1及PARP表达下降,且A549/DDP组PARP蛋白表达下调更明显(P<0.05)。结论:BI2536可抑制顺铂耐药的A549/DDP细胞增殖,并诱导其凋亡,其作用机制可能与抑制PLK1及PARP表达有关。OBJECTIVE To investigate the anti-proliferative effect of BI2536 on human non-small cell lung cancer （NSCLC） cells A549 and cisplatin-resistance A549/DDP in vitro, METHODS Human NSCLC cells A549 and A549/DDP were treated with different concentrations of BI2536. 48 hours later, MTT assay was used to determine the cells proliferation, flow cytometry was employed to assess the apoptosis of the treated cells, and expression of PLK1 and PARP protein was measured by Western blot. RESULTS BI2536 was demonstrated to have stronger inhibitory effect on the proliferation of A549 / DDP cells with IC50 of （9.9 ± 0. 4）nmol·L -1 than that on A549 cells with IC50 of （25.9 ± 1.03） nmol·L -1 （P〈0. 01）. After 20 nmol.L 1 of 1312536 treatment, the apoptosis rate of A549/DDP was significantly higher than that of A549 cells by using flow cytometry （60. 6% vs 20. 3%, P〈0. 01）. The expressions of PLK1 and PARP were both down-regulated in dose-dependent manner. Interestingly, the down-regulation of PARP in A549/DDP cells was more significant （P〈0. 05）. CONCLUSION BI2536 could inhibit the proliferation and induce the apoptosis of cisplatin-resistance NSCLC cells A549 / DDP. The probable mechanism may be related to the down-regulation of PLK1 and PARP.

关 键 词：BI2536 顺铂 非小细胞肺癌 耐药 

分 类 号：R969[医药卫生—药理学]