[1]任祥春,季 爽,张文英,等.雌二醇调控VEGFα表达诱导肺腺癌A549细胞血管形成[J].中国药理学通报,2019,(09):1262-1266.[doi:10.3969/j.issn.1001-1978.2019.09.015]
 REN Xiang-chun,JI Shuang,ZHANG Wen-ying,et al.Regulation of VEGFα expression by 17β-estradiol induced angiogenesis in lung adenocarcinoma[J].Chinese Pharmacological Bulletin,2019,(09):1262-1266.[doi:10.3969/j.issn.1001-1978.2019.09.015]
点击复制

雌二醇调控VEGFα表达诱导肺腺癌A549细胞血管形成()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年09期
页码:
1262-1266
栏目:
论著
出版日期:
2019-09-09

文章信息/Info

Title:
Regulation of VEGFα expression by 17β-estradiol induced angiogenesis in lung adenocarcinoma
文章编号:
1001-1978(2019)09-1262-05
作者:
任祥春季 爽张文英费广鹤
安徽医科大学第一附属医院呼吸与危重症医学科,安徽 合肥 230022
Author(s):
REN Xiang-chun JI Shuang ZHANG Wen-ying FEI Guang-he
Dept of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
关键词:
雌二醇 雌激素受体 肺腺癌 VEGFα 迁移 血管形成
Keywords:
17β-estradiol estrogen receptor lung adenocarcinoma VEGFα migration angiogenesis
分类号:
R329.24; R364.3; R392.11; R734.202.2; R977.12
DOI:
10.3969/j.issn.1001-1978.2019.09.015
文献标志码:
A
摘要:
目的 研究雌二醇(17β-estradiol,E2)在肺腺癌A549细胞微环境中,通过血管内皮生长因子α(vascular endothelial growth factor α,VEGFα)诱导肿瘤血管形成的发生机制。方法 将A549细胞分为3组:PBS组、10 nmol·L-1 E2组、10 nmol·L-1 E2+5 μmol·L-1雌激素受体拮抗剂(ICI)组。Western blot和ELISA法检测肺腺癌A549细胞和培养基中VEGFα的表达; MTT法检测人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)的增殖能力; 划痕实验检测HUVEC细胞迁移能力; 小管生成实验检测HUVEC细胞的体外血管生成能力。结果 与对照组(PBS)相比,E2刺激后的A549细胞中VEGFα的表达量增加,而加入ICI后,VEGFα表达量明显下降; 同时,E2诱导A549细胞及上清液中VEGFα的表达,促进了HUVEC细胞的增殖、迁移和小管形成能力,ICI则相反。结论 E2通过作用于A549细胞中雌激素受体,刺激肺腺癌微环境中VEGFα的表达,促进肺腺癌血管内皮细胞的增殖、迁移和小管形成能力,诱导肺腺癌血管形成。
Abstract:
AimTo investigate the mechanism of 17β-estradiol(E2)induced tumor angiogenesis by VEGFα in the microenvironment of lung adenocarcinoma in A549 cells.Methods A549 cells were divided into three groups: PBS group, 10 nmol·L-1 E2 group and 10 nmol·L-1 E2 +5 μmol·L-1 estrogen receptor antagonist(ICI)group.Western blot was used to detect the expression of VEGFα in A549 cells, and ELISA was used to detect the expression of VEGFα in culture medium.The proliferation of human umbilical vein endothelial cells(HUVECs)was detected by MTT, the migration ability of HUVECs by scratch assay and the tubulogenesis in vitro by tube formation assay.Results Compared with control group, the expression of VEGFα in A549 cells in E2 group was higher, but the expression of VEGFα in A549 cells was significantly inhibited with the addition of ICI.Meanwhile, E2 induced the expression of VEGFα in A549 cells, promoting proliferation, migration and tubulogenesis of HUVEC, while ICI had the opposite effects.Conclusions E2 stimulates the expression of VEGFα by binding to estrogen receptor in A549 cells, promoting proliferation, migration and tube formation of HUVECs, contributing to lung adenocarcinoma angiogenesis.

参考文献/References:

[1] Chen W, Zheng R, Baade P D, et al.Cancer statistics in China, 2015[J].CA Cancer J Clin, 2016,66(2):115-32.
[2] Kinoshita F L, Ito Y, Morishima T, et al.Sex differences in lung cancer survival: long-term trends using population-based cancer registry data in Osaka, Japan[J].Jpn J Clin Oncol, 2017,47(9):863-9.
[3] Donington J S, Colson Y L.Sex and gender differences in non-small cell lung cancer[J].Semin Thorac Cardiovasc Surg, 2011,23(2):137-45.
[4] Fan S,Liao Y,Liu C,et al.Estrogen promotes tumor metastasis via estrogen receptor beta-mediated regulation of matrix-metalloproteinase-2 in non-small cell lung cancer[J].Oncotarget, 2017,8(34):56443-59.
[5] 李婷婷,费广鹤.绝经前女性肺腺癌患者ERβ的表达及临床意义[J].临床肺科杂志, 2016, 21(7):1299-302.
[5] Li T T, Fei G H.The expression of ERβ in lung adenocarcinoma and its clinical significance[J].J Clin Pulm Med, 2016,21(7):1299-302.
[6] Wu J B,Tang Y L.Targeting VEGF pathway to normalize the vasculature: an emerging insight in cancer therapy[J].Onco Targets Ther, 2018,11(10):6901-9.
[7] Frezzetti D,Gallo M, Maiello M R,et al.VEGF as a potential target in lung cancer[J].Expert Opin Ther Targets, 2017,21(10):959-66.
[8] Siegfride J M, Stabile L P.Estrongenic steroid hormones in lung cancer[J].Semin Oncol, 2014, 41(1): 5-16.
[9] 韩 翰,王 敏.SAHA和TRAIL联合使用对乳腺癌雌激素受体阳性细胞MCF-7生长的影响[J].中国药理学通报, 2016,32(2):223-8.
[9] Han H,Wang M.Effects of combination treatment with SAHA and TRAIL on ER positive breast cancer cell MCF-7[J].Chin Pharmacol Bull, 2016,32(2):223-8.
[10] 赵丕文, David Yue-Wei Lee,陶仕英,等.G蛋白偶联雌激素受体在雌激素相关肿瘤发生中的作用[J].中国药理学通报, 2014,30(8):1037-41.
[10] Zhao P W,Lee D Y,Tao S Y, et al.Effect of G protein-coupled estrogen receptor on the occurrence and development of estrogen related cancer[J].Chin Pharmacol Bull, 2014,30(8): 1037-41.
[11] Wang C,Li J,Ye S,et al.Oestrogen inhibits VEGF expression and angiogenesis in triple-negative breast cancer by activating GPER-1[J].J Cancer, 2018,9(20):3802-11.
[12] DeFrancesco E M, Pellegrino M, Santolla M F, et al.GPER mediates activation of HIF1alpha/VEGF signaling by estrogens[J].Cancer Res, 2014,74(15): 4053-64.
[13] Kamat A, Rajoria S, George A, et al.Estrogen-mediated angiogenesis in thyroid tumor microenvironment is mediated through VEGF signaling pathways[J].Arch Otolaryngol Head Neck Surg, 2011,137(11): 1146-53.
[14] Siegfried J M,Gubish C T,Rothstein M E,et al.Combining the multitargeted tyrosine kinase inhibitor vandetanib with the antiestrogen fulvestrant enhances its antitumor effect in non-small cell lung cancer[J].J Thorac Oncol, 2012,7(3):485-95.

相似文献/References:

[1]张夏微,张丹参,薛贵平,等.蛇床子素对大鼠雌激素样作用的实验研究[J].中国药理学通报,2013,(07):1031.
 ZHANG Xia wei,ZHANG Dan shen,XUE Gui ping,et al.Experimental research on estrogenic effect of Osthole on rats[J].Chinese Pharmacological Bulletin,2013,(09):1031.
[2]赵丕文,David Yue-Wei Lee,陶仕英,等.G蛋白偶联雌激素受体在雌激素相关肿瘤发生中的作用[J].中国药理学通报,2014,(08):1037.
 ZHAO Pi-wen,David Yue-Wei Lee,TAO Shi-ying,et al.Effect of G protein-coupled estrogen receptor on the occurrence and development of estrogen related cancer[J].Chinese Pharmacological Bulletin,2014,(09):1037.
[3]雷 静,陈飞虎,葛金芳,等.4-氨基-2-三氟甲基苯基维甲酸酯对人乳腺癌细胞株MDA-MB-231诱导分化作用及可能的机制研究[J].中国药理学通报,2015,(07):973.[doi:10.3969/j.issn.1001-1978.2015.07.017]
 LEI Jing,CHEN Fei-hu,GE Jin-fang,et al.Inducing effect of 4-Amino-2-Trifluoromethyl-Phenyl Retinate on differentiation of human breast cancer MDA-MB-231 cell and its possible mechanisms[J].Chinese Pharmacological Bulletin,2015,(09):973.[doi:10.3969/j.issn.1001-1978.2015.07.017]
[4]于庆龙,张 莹,王宏健,等.17β-雌二醇对乳腺癌细胞迁移的影响及CANP-FN通路的介导作用[J].中国药理学通报,2017,(10):1371.[doi:10.3969/j.issn.1001-1978.2017.10.009]
 YU Qing-long,ZHANG Ying,WANG Hong-jian,et al.Role of calpain-fibronectin signaling in estrogen-induced migration in breast cancer cells[J].Chinese Pharmacological Bulletin,2017,(09):1371.[doi:10.3969/j.issn.1001-1978.2017.10.009]
[5]韩杜菀,郑晓珂,赵莹莹,等.葶苈子雌激素样活性筛选及其作用机制研究[J].中国药理学通报,2018,(07):953.[doi:10.3969/j.issn.1001-1978.2018.07.013]
 HAN Du-wan,ZHENG Xiao-ke,ZHAO Ying-ying,et al.Evaluation of estrogenic effects of Semen Descurainiae and its action mechanism[J].Chinese Pharmacological Bulletin,2018,(09):953.[doi:10.3969/j.issn.1001-1978.2018.07.013]

备注/Memo

备注/Memo:
收稿日期:2019-04-20,修回日期:2019-06-18
基金项目:安徽省重点研究和开发计划项目(No 1804h08020237); 合肥市自主创新“借转补”项目(No J2018Y04)
作者简介:任祥春(1988-),男,硕士生,研究方向:肺癌发病机制,E-mail: rxc2006@126.com;
费广鹤(1964-),男,博士,教授,博士生导师,研究方向:肺癌发病机制,通讯作者,E-mail: guanghefei@126.com
更新日期/Last Update: 2019-08-14