广藿香酮通过JNK/c-Jun信号通路调控肺癌A549细胞凋亡及自噬  

Pogostone regulates apoptosis and autophagy in lung cancer A549 cells through the JNK/c-Jun signaling pathway

作　　者：郑晓燕 王宇琛[1] 张丽美 韩媛媛[1] 冀芮 姜伟华[1] ZHENG Xiaoyan;WANG Yuchen;ZHANG Limei;HAN Yuanyuan;JI Rui;JIANG Weihua(Department of Thoracic Surgery,The First Affiliated Hospital of Hebei North University,Zhangjiakou 075000,China)

机构地区：[1]河北北方学院附属第一医院胸外科,河北张家口075000

出　　处：《临床肿瘤学杂志》2023年第5期392-398,共7页Chinese Clinical Oncology

基　　金：河北省医学科学研究课题(20211359)。

摘　　要：目的探讨广藿香酮对肺癌A549细胞增殖、凋亡、自噬和JNK/c-Jun信号通路的影响。方法采用0、10、20、40μmol/L广藿香酮处理肺癌A549细胞,将细胞随机分为4组:0μmol/L、10μmol/L、20μmol/L和40μmol/L广藿香酮处理组,同时将5μmol/L顺铂处理后的肺癌A549细胞作为阳性对照组。EdU染色检测细胞增殖;Hoechst 33258染色检测细胞凋亡;Western blotting检测LC3Ⅰ、LC3Ⅱ、Beclin-1、p62、JNK、p-JNK、c-Jun和p-c-Jun蛋白表达。10μmol/L JNK抑制剂SP600125与40μmol/L广藿香酮共处理A549细胞2 h及24 h,检测细胞增殖、凋亡及相关蛋白表达。结果与广藿香酮0μmol/L组比较,广藿香酮20、40μmol/L组EdU阳性细胞数降低,细胞凋亡率升高,LC3Ⅱ/LC3Ⅰ比值和Beclin-1蛋白表达升高,p62蛋白表达降低,LC3+含量升高,p-JNK/JNK、p-c-Jun/c-Jun比值升高,差异均有统计学意义(P<0.05)。与对照组比较,SP600125组p-JNK/JNK、p-c-Jun/c-Jun、LC3Ⅱ/LC3Ⅰ比值、细胞凋亡率及Beclin-1蛋白表达显著降低,EdU阳性细胞数、p62蛋白表达显著升高,差异均有统计学意义(P<0.05)。与SP600125组比较,广藿香酮40μmol/L+SP600125组p-JNK/JNK、p-c-Jun/c-Jun、LC3Ⅱ/LC3Ⅰ比值、细胞凋亡率及Beclin-1蛋白表达显著升高,EdU阳性细胞数、p62蛋白表达显著降低,差异均有统计学意义(P<0.05)。结论广藿香酮通过JNK/c-Jun信号通路抑制肺癌A549细胞增殖,诱导细胞凋亡及自噬。Objective To investigate the effects of pogostone on apoptosis,autophagy and JNK/c-Jun signaling pathway in lung cancer A549 cells.Methods Lung cancer A549 cells were treated with 0,10,20,and 40μmol/L pogostone and randomly divided into 4 groups:0μmol/L,10μmol/L,20μmol/L and 40μmol/L pogostone group.A549 cells treated with 5μmol/L cisplatin were used as positive control group.EdU staining was used to detect the ability of cell proliferation.Hoechst 33258 staining was used to detect cell apoptosis.The protein expressions of LC3Ⅰ,LC3Ⅱ,Beclin-1,p62,JNK,p-JNK,c-Jun and p-c-Jun were detected by Western blotting.Lung cancer A549 cells were treated with 10μmol/L JNK inhibitor SP600125 and 40μmol/L pogostone for 2 h and 24 h,cell proliferation,apoptosis and related protein expression were detected.Results Compared with 0μmol/L pogostone group,the number of EdU positive cells and p62 protein expression were decreased,the cell apoptotic rate,LC3Ⅱ/LC3Ⅰratio,Beclin-1 protein expression,LC3+content and p-c-Jun/c-Jun ratios was increased in 20 and 40μmol/L pogostone group,and the difference between groups was statistically significant(P<0.05).Compared with the control group,the p-JNK/JNK,p-c-Jun/c-Jun,LC3Ⅱ/LC3Ⅰratios,apoptotic rate and Beclin-1 protein expression were significantly decreased in SP600125 group,while the number of EdU positive cells and p62 protein expression were significantly increased,and the difference between groups was statistically significant(P<0.05).Compared with SP600125 group,p-JNK/JNK,p-c-Jun/c-Jun,LC3Ⅱ/LC3Ⅰratios,apoptotic rate and Beclin-1 protein expression were significantly increased in 40μmol/L pogostone+SP600125 group,while EdU positive cell number and p62 protein expression were significantly decreased,and the difference between groups was statistically significant(P<0.05).Conclusion Pogostone can inhibit the proliferation and induce apoptosis and autophagy of lung cancer A549 cells through JNK/c-Jun signaling pathway.

关 键 词：肺癌 广藿香酮 凋亡 自噬 JNK/c-Jun信号通路 

分 类 号：R734.2[医药卫生—肿瘤]