和厚朴酚通过NF-κB信号通路抑制IL-1诱导的人肺癌细胞H460血管生成  

Honokiol inhibits IL-1 induced angiogenesis in human lung cancer cell H460 through NF-κB signaling pathway

作　　者：成旭东[1] 陈婷[1] 范玲 林梦 陈汀[1] 于栋伟 唐樑[1] 沈夕坤[1] 黄玉宇 CHENG Xu-dong;CHEN Ting;FAN Ling;LIN Meng;CHEN Ting;YU Dong-wei;TANG Liang;SHEN Xi-kun;HUANG Yu-yu(Suzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Suzhou Jiangsu 215009, China;Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou Jiangsu 215101, China)

机构地区：[1]南京中医药大学附属苏州市中医医院,江苏苏州215009 [2]苏州市中西医结合医院,江苏苏州215101

出　　处：《中国药理学通报》2022年第3期380-386,共7页Chinese Pharmacological Bulletin

基　　金：江苏省自然科学基金资助项目(No BK20171226);江苏省青年医学人才项目(No QNRC2016251);苏州科技计划项目(No SYS2020184);南京中医药大学自然科学基金项目(No XZR2020040)。

摘　　要：目的探讨和厚朴酚(honokiol,HNK)对肿瘤炎性微环境诱导的肺癌细胞H460血管生成的影响及其可能的机制。方法采用CCK-8检测HNK对H460细胞和人脐静脉内皮细胞(HUVECs)增殖的影响;RT-PCR、Western blot、免疫荧光检测血管内皮生长因子(VEGF)的表达;Western blot检测信号通路蛋白p-IκBα、p-IKKα和NF-κB p65蛋白表达。采用划痕试验、Transwell迁移试验和成管试验检测HNK抑制HUVEC细胞的迁移和血管生成能力。结果HNK作用H460细胞24、48、72 h后,浓度和时间依赖地抑制H460细胞增殖。HNK能够浓度依赖的抑制HUVEC细胞的存活。HNK还降低了H460细胞中血管内皮生长因子(VEGF)的蛋白质和mRNA表达水平。随后,HNK浓度依赖性地抑制了NF-κB信号通路中IκBα、NF-κB和p-IKKα。划痕试验、Transwell小室迁移试验和成管试验显示HNK处理的H460条件培养基具有抑制HUVEC细胞的迁移和血管生成能力。结论HNK可以通过抑制NF-κB途径导致VEGF的下调而降低人肺癌细胞的活力和血管生成。Aim To investigate the effect of honokiol(HNK)on the angiogenesis of lung cancer cells H460 induced by the tumor inflammatory microenvironment and its possible mechanism.Methods CCK-8 was used to detect the effect of HNK on the proliferation of H460 cells and human umbilical vein endothelial cells(HUVECs);RT-PCR,Western blot,immunofluorescence were used to detect the expression of vascular endothelial growth factor(VEGF);Western blot was used to detect the signaling pathway protein p-IκBα,p-IKKαand NF-κB p65 protein expression.The wound healing test,transwell and tube formation tests were used to detect the inhibition ability of HNK on the migration and angiogenesis of HUVECs.Results HNK treated H460 cells for 24,48,72 h respectively,and inhibited the proliferation of H460 cells in a concentration-and time-dependent manner.HNK inhibited the survival of HUVEC cells in a concentration-dependent manner.HNK also reduced the protein and mRNA expression levels of VEGF in H460 cells.Subsequently,HNK concentration-dependently inhibited the phosphorylation of IκBα,NF-κB and IKKαin the NF-κB signaling pathway.Wound healing test,Transwell cell migration test and tube formation test showed that H460 conditioned medium treated with HNK had the ability to inhibit the migration and angiogenesis of HUVECs.Conclusions HNK reduces the viability and angiogenesis of human lung cancer cells by down-regulation of VEGF via the NF-κB pathway.

关 键 词：和厚朴酚 肺癌细胞 血管生成 血管内皮生长因子 NF-ΚB H460 

分 类 号：R284.1[医药卫生—中药学] R285.5[医药卫生—中医学]