川芎嗪通过调控 Wnt信号通路抑制肺癌细胞增殖、侵袭和迁移的机制研究  

Mechanism of tetramethylpyrazine inhibiting proliferation,invasion and migration of lung cancer cells by regulating Wnt signaling pathway

作　　者：李高兵 蔡东平 毛张凡[3] Li Gaobing;Cai Dongping;Mao Zhangfan(Pulmonary Disease Department ,Xiangyang Hospital of Traditional Chinese Medicine , Hubei Xiangyang 441000 , China;Occupational Disease Department ,Xiangyang Occupational Disease Prevention and Cure Lnstitute, Hubei Xiangyang 441000, China;Thoracic Surgery,Renmin Hospital of Wuhan University, Hubei Wuhan 430000, China)

机构地区：[1]襄阳市中医医院肺病科,湖北襄阳441000 [2]襄阳市职业病防治院职业病科,湖北襄阳441000 [3]武汉大学人民医院胸外科,湖北武汉430000

出　　处：《现代肿瘤医学》2019年第12期2035-2040,共6页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:81101627)

摘　　要：目的:探讨川芎嗪通过调控Wnt信号通路影响人肺癌A549细胞增殖、侵袭和迁移的机制研究。方法:将培养的人肺癌细胞A549随机分为四组:对照组、川芎嗪组、抑制剂组、川芎嗪+抑制剂组,噻唑蓝(MTT)法检测各组A549细胞增殖能力,流式细胞术检测各组A549细胞生长周期,Transwell实验检测各组A549细胞侵袭能力,划痕实验检测各组A549细胞迁移能力,蛋白免疫印迹(Western blot)检测各组A549细胞中β-连环蛋白(β-catenin)、c-myc、增殖细胞核抗原(PCNA)和基质金属蛋白酶-9(MMP-9)蛋白水平。结果:与对照组相比,川芎嗪组和抑制剂组均能够抑制A549细胞增殖,阻滞细胞周期至G_1期,阻碍细胞侵袭和迁移,下调细胞中β-catenin、c-myc、PCNA和MMP-9蛋白水平,差异具有统计学意义(P<0.05)。与川芎嗪组和抑制剂组相比,川芎嗪+抑制剂组A549细胞增殖能力显著降低,细胞周期阻滞于G_1期,细胞侵袭和迁移能力受到抑制,细胞中β-catenin、c-myc、PCNA和MMP-9蛋白水平显著降低,差异具有统计学意义(P <0. 05)。结论:川芎嗪能够抑制人肺癌细胞A549细胞的增殖、侵袭和迁移,其作用机制与抑制Wnt信号通路的激活有关。Objective:To investigate the mechanism of tetramethylpyrazine on the proliferation,invasion and migration of human lung cancer A549 cells by regulating Wnt signaling pathway.Methods:Human lung cancer cells A549 were randomly divided into four groups:control group,tetramethylpyrazine group,inhibitor group,tetramethylpyrazine+inhibitor group.MTT assay was used to detect the proliferation of A549 cells.The growth cycle of A549 cells was detected by Transwell assay.The invasion ability of A549 cells was detected by Transwell assay.The migration ability of A549 cells was detected by scratch test.The β-catenin(β-catenin) in A549 cells was detected by Western blot),c-myc,proliferating cell nuclear antigen(PCNA) and matrix metalloproteinase-9(MMP-9) protein levels.Results:Compared with the control group,both the tetramethylpyrazine group and the inhibitor group could inhibit the proliferation of A549 cells,block the cell cycle to the G1 phase, hinder cell invasion and migration,and down-regulate β-catenin,c-myc,PCNA and MMP in cells,the difference was statistically significant(P<0.05).Compared with the tetramethylpyrazine group and the inhibitor group,the proliferative ability of the tetramethylpyrazine+inhibitor group A549 cells was significantly decreased,the cell cycle was arrested in the G1 phase,and the cell invasion and migration ability was inhibited.The levels of PCNA and MMP-9 protein were significantly lower,and the difference was statistically significant(P<0.05).Conclusion:Tetramethylpyrazine can inhibit the proliferation,invasion and migration of human lung cancer cell line A549,and its mechanism is related to the inhibition of Wnt signaling pathway activation.

关 键 词：川芎嗪 WNT信号通路 细胞增殖 侵袭 迁移 

分 类 号：R734.2[医药卫生—肿瘤]