信号转导及转录激活因子3在紫铆因诱导人肺腺癌A549细胞凋亡作用的研究  

Butein exerts pro-apoptotic activity in lung adenocarcinoma A549 cells via the regulation of STAT3 signaling

作　　者：陈少阳 岳宏林 刘旭 

机构地区：[1]陆军总医院二六三临床部重症监护室,北京101149

出　　处：《中国医药导报》2017年第21期29-33,共5页China Medical Herald

摘　　要：目的探讨紫铆因(BTN)诱导人肺腺癌A549细胞凋亡的作用及信号转导及转录激活因子3(STAT3)在该过程发挥的作用。方法常规培养A549细胞,给予0、25、50μmol/L的BTN处理24 h,BTN 0μmol/L为对照组,检测各组细胞活力、凋亡、迁移、ROS含量及Caspase-3活性,STAT3通路(p-STAT3、STAT3)和凋亡相关蛋白(Bcl-2、Bax)含量变化。N-乙酰-L-半胱氨酸(NAC)5 mmol/L特异性抑制活性氧(ROS)生成后,BTN(0、50μmol/L)处理细胞24 h,重复上述检测。建立裸鼠皮下肿瘤模型,腹腔注射BTN(2、4 mg/kg),对照组注射等体积PBS,明确BTN抗肺腺癌的作用。结果与对照组相比,BTN(25、50μmol/L)有效抑制A549细胞活力和迁移(P<0.05),促进凋亡(P<0.05),显著增加ROS含量及Caspase-3活性(P<0.05)。Western blot结果显示,相比对照组,BTN处理抑制p-STAT3和Bcl-2表达(P<0.05),上调凋亡蛋白Bax表达(P<0.05)。相比BTN组,应用NAC后则抑制BTN促ROS生成(P<0.05),同时拮抗了BTN抑制STAT3磷酸化和促凋亡作用(P<0.05)。在体研究发现,相比对照组,BTN处理剂量依赖地抑制肿瘤生长,抑制STAT3磷酸化(P<0.05)。结论 BTN可有效抑制肺腺癌A549细胞活力、促进细胞凋亡,此作用可能与促ROS生成进而抑制STAT3磷酸化有关。Objective To investigate the pro-apoptotic effect of Butein（BTN） in lung adenocarcinoma A549 cells and the role of STAT3 signaling in this process. Methods A549 cells were cultured and treated with different concentrations of BTN（0, 25, 50 μmol/L） for 24 h. BTN 0 μmol/L was taken as the control group. The survival rate, apoptotic rate, cell migration, ROS generation, Caspase-3 activity were respectively detected after treatment. Western blot was used to detect expression of p-STAT3, STAT3, Bcl-2 and Bax. NAC 5 mmol/L was used to block the generation of ROS, then BTN treatment（0, 50 μmol/L） was implemented for further detection as mentioned. Besides, in vivo studies were also used to verify whether abdominal injection with BTN（2, 4 mg/kg） exerted anticancer activity, while the control group was injected with PBS. Results Compared with the control group, BTN（25, 50 μmol/L） treatment resulted in reduction of cell viability and migration（P〈0.05）, promotion of cell apoptosis（P〈0.05）, up-regulation of ROS and Caspase-3 levels（P〈0.05）. BTN treatment resulted in a significant down-regulation of p-STAT3 and Bcl-2, and upregulation of Bax（P〈0.05）. Moreover, inhibition of ROS by NAC antagonized the anti-STAT3 phosphorylated and pro-apoptotic role of BTN on A549 cells（P〈0.05）. In vivo studies showed that compared the control group, tumor volume and p-STAT3 expression in nude mice were significantly reduced after BTN treatment（P〈0.05）. Conclusion BTN treatment effectively inhibits cell viability and promotes apoptosis in A549 cells, which may be related to the upregulation of ROS level thus inhibiting STAT3 phosphorylation.

关 键 词：紫铆因 肺腺癌 信号转导及转录激活因子3 活性氧 凋亡 

分 类 号：R734.2[医药卫生—肿瘤]