羟氯喹对肺癌细胞恶性生物学行为影响  

Effect of hydroxychloroquine on malignant biological behavior of lung cancer cells

作　　者：吴水发 傅新阳[1] 黄晓威[1] 洪磊 陈婷婷[1] WU Shui-fa;FU Xin一yang;HUANG Xiao-wei;HONG Lei;CHEN Ting-ting(Department of Pharmacy,Quanzhou First Hospital filiated to Fujian Medical University,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属泉州第一医院药剂科,福建泉州362000

出　　处：《中国临床药理学杂志》2020年第21期3493-3496,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨羟氯喹对肺癌细胞恶性生物学行为及细胞外信号调节激酶(ERK)-血管内皮生长因子(VEGF)/基质金属蛋白酶-9(MMP-9)信号通路的影响。方法体外培养人肺腺癌A549细胞,取对数期人肺腺癌A549细胞分为低、中、高剂量实验组与对照组,分别以20,40,80μmol·L-1羟氯喹与等量生理盐水处理,各组均干预12,24,48 h。用Transwell实验及划痕实验分别检测人肺腺癌A549细胞侵袭与迁移能力;用噻唑蓝(MTT)法检测人肺腺癌A549细胞增殖;用蛋白质印迹(Wb)法检测人肺腺癌A549细胞ERK、VEGF及MMP-9蛋白的表达水平。结果干预48 h时,对照组与低、中、高剂量实验组人肺腺癌A549细胞侵袭率分别为(78.21±4.32)%,(50.22±3.14)%,(21.37±4.06)%,(8.95±3.73)%;划痕闭合率分别为(76.32±4.11)%,(64.52±3.96)%,(47.36±4.02)%,(21.64±5.21)%;ERK蛋白相对表达量分别为0.92±0.08,0.71±0.14,0.39±0.10,0.17±0.05;VEGF蛋白相对表达量分别为0.93±0.07,0.47±0.11,0.33±0.09,0.12±0.03;MMP-9蛋白相对表达量分别为0.91±0.09,0.68±0.12,0.41±0.13,0.09±0.02,差异均有统计学意义(均P<0.05)。结论羟氯喹可呈剂量依赖性地抑制人肺腺癌A549细胞增殖、侵袭和迁移能力,其作用机制可能与下调人肺腺癌A549细胞ERK、VEGF、MMP-9蛋白表达,抑制ERK-VEGF/MMP-9通路信号转导相关。Objective To investigate the effect of hydroxychloroquine on malignant biological behavior of lung cancer cells and extracellular signal-regulated kinase(ERK)-vascular endothelial growth factor(VEGF)/matrix metalloproteinase-9(MMP-9)signaling pathway.Methods Human lung adenocarcinoma A549 cells were cultured in vitro,logarithmic human lung adenocarcinoma A549 cells were divided into Exp-L,Exp-M,Exp-H groups and control group,treated with 20,40,80μmol·L-1 hydroxychloroquine and equal amount of normal saline.Each group was intervened for 12,24,48 h.Transwell test and scratch test were used to detect the invasion and migration ability of human lung adenocarcinoma A549 cells;the proliferation of human lung adenocarcinoma A549 cells was detected by methyl thiazolyl tetrazolium(MTT)method;Western blotting(Wb)method was used to detect the expression levels of ERK,VEGF and MMP-9 in human lung adenocarcinoma A549 cells.Results At 48 h of intervention,the invasion rates of human lung adenocarcinoma A549 cells in control group and Exp-L,-M,-H groups were(78.21±4.32)%,(50.22±3.14)%,(21.37±4.06)%,(8.95±3.73)%;the scratch closure rates were(76.32±4.11)%,(64.52±3.96)%,(47.36±4.02)%,(21.64±5.21)%;the relative expression levels of ERK protein were 0.92±0.08,0.71±0.14,0.39±0.10,0.17±0.05;the relative expression levels of VEGF protein were 0.93±0.07,0.47±0.11,0.33±0.09,0.12±0.03;the relative expression levels of MMP-9 protein were 0.91±0.09,0.68±0.12,0.41±0.13,0.09±0.02,all with significant differences(all P<0.05).Conclusion Hydroxychloroquine can dose-dependently inhibit the proliferation,invasion and migration of human lung adenocarcinoma A549 cells,and the mechanism may be related to the down-regulation of ERK,VEGF,MMP-9 protein expression in human lung adenocarcinoma A549 cells,and inhibition of ERK-VEGF/MMP-9 pathway signal transduction.

关 键 词：羟氯喹 恶性生物学行为 人肺腺癌A549细胞 侵袭 迁移 细胞外信号调节激酶 血管内皮生长因子 基质金属蛋白酶-9 

分 类 号：R979.1[医药卫生—药品]