8-Br-cAMP联合顺铂作用于肺腺癌细胞A549的初步研究  

Synergistic effect of 8-Br-cAMP and cisplatin in human pulmonary adenocarcinoma cell A549

作　　者：陈曦[1] 刘志勇[1,2] 

机构地区：[1]东南大学临床医学院,江苏南京210009 [2]东南大学附属中大医院胸心外科,江苏南京210009

出　　处：《东南大学学报（医学版）》2010年第2期193-198,共6页Journal of Southeast University(Medical Science Edition)

摘　　要：目的:观察8-溴-环腺苷酸(8-Br-cAMP)联合顺铂(DDP)对人肺腺癌细胞A549生长及其表皮生长因子受体(EGFR)表达的影响。方法:MTT法测定不同浓度8-Br-cAMP、DDP以及两药联用处理人肺腺癌细胞A549后细胞增殖活性的差异;应用RT-PCR技术检测EGFR mRNA表达水平的变化;Western blot技术检测EGFR蛋白表达水平的变化;利用流式细胞术测定细胞周期的改变。结果:8-Br-cAMP及DDP均能抑制人肺腺癌细胞A549的增殖,并呈浓度及时间依赖性;DDP联合8-Br-cAMP细胞抑制率显著高于相应浓度单药组(P<0.05),两者呈现出相加的抗瘤效果。8-Br-cAMP可下调人肺腺癌A549细胞EGFR mRNA和蛋白的表达。8-Br-cAMP将细胞周期阻滞在G2/M期(P<0.05)。结论:8-Br-cAMP、DDP均可抑制A549细胞增殖。8-Br-cAMP可显著提高顺铂的细胞毒作用,增强化疗效果,并将细胞阻滞于G2/M期。8-Br-cAMP可以下调EGFR表达,可一定程度地逆转化癌细胞。Objective： To study the effect of 8-Br-cAMP with cisplatin（DDP） on human pulmonary adenocarcinoma cell A549 growth and the expression level of EGFR in vitro.Methods： Proliferation ability and cell cycle changes of A549 cells were detected by MTT method and flow cytometry.The mRNA levels of EGFR were determined by RT-PCR.The protein expression of EGFR were valued by Western blot.Results： Both DDP and 8-Br-cAMP could inhibit the proliferation of A549 cells in vitro by a time-and dose-dependent manner.Compared with either 8-Br-cAMP or DDP alone,combining 8-Br-cAMP at 15 μmol·L-1 with DDP at 0.5 μg·ml-1,1 μg·ml-1,2 μg·ml-1,4 μg·ml-1 respectively increased the growth inhibition rate of A549 cells significantly（P0.05）.These results suggested additive actions of the two drugs.A549 cells showed G2/M stage arrest after 8-Br-cAMP administration（P0.05）.Compared with the control group,expression of EGFR mRNA and EGFR protein significantly decreased in the 8-Br-cAMP group and combining 8-Br-cAMP with DDP group.Conclusions： Both DDP and 8-Br-cAMP could inhibit the proliferation of lung cancer cells in vitro.8-Br-cAMP has also shown synergistic antitumor effects when combined with DDP.8-Br-cAMP can decrease the expression of EGFR and block the cell cycle at G2/M stage.

关 键 词：8-溴-环腺苷酸 肺腺癌细胞A549 表皮生长因子受体 蛋白激酶A 

分 类 号：R734.2[医药卫生—肿瘤] R329.28[医药卫生—临床医学]