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《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:

期数:

2021年05期

页码:

573-578

栏目:

论著

出版日期:

2021-10-20

文章信息/Info

Title:

Silencing HIF-1α regulates MAPK/ERK pathway and inhibits metastasis of NSCLC

作者:

余治国¹; 巩 博¹; 陆卫华¹; 李鸣芳²

430014 武汉,中部战区总医院急诊科¹、肿瘤科²

Author(s):

Yu Zhiguo¹;  Gong Bo¹;  Lu Weihua¹;  Li Minfang².

Emergency Department¹, Oncology Department², Central Theater Command General Hospital, Wuhan 430014, China

关键词:

HIF-1α;  MAPK/ERK;  转移;  非小细胞肺癌

Keywords:

HIF-1α;  MAPK/ERK;  Metastasis;  Non-small cell lung cancer

分类号:

R734.2

DOI:

10.3877/cma.j.issn.1674-6902.2021.05.006

摘要:

目的 探讨HIF-1α在体内及体外对非小细胞肺癌(NSCLC)细胞转移的影响及其作用机制。方法 采用实时荧光定量PCR(RT-qPCR)检测HIF-1α在癌旁正常组织、肺鳞癌组织(LUSC)、肺腺癌组织(LUAD)、A549细胞和HEB细胞中的表达量。上调HIF-1α表达后,通过MTT、细胞侵袭和Western blot实验检测过表达HIF-1α对A549细胞增殖、侵袭和EMT的影响。下调HIF-1α表达后,Western blot检测A549细胞ERK和p-ERK蛋白的表达量。THBQ激活MAPK/ERK通路后,分析A549细胞增殖、侵袭和EMT能力。将细胞株植入裸鼠体内,构建移植瘤模型,最后测量裸鼠移植瘤的体积和重量。结果 HIF-1α在NSCLC组织的表达水平明显高于癌旁正常组织(P<0.05)。A549细胞中HIF-1α表达水平明显高于HEB细胞(P<0.01),过能够促进A549细胞的增殖和侵袭,N-cadherin蛋白表达量明显上升,E-cadherin蛋白表达量明显下降。下调HIF-1α能够抑制A549细胞内MAPK/ERK通路,且抑制了A549细胞的增殖、侵袭和EMT。下调HIF-1α使裸鼠移植瘤的重量和体积明显减小。结论 沉默HIF-1α通过MAPK/ERK信号通路在体内及体外抑制NSCLC转移。

Abstract:

Objective To investigate the effects of HIF-1α on metastasis of non-small cell lung cancer and its mechanism in vitro and in vivo. Methods Quantitative real-time PCR(RT-qPCR)was used to detect the expression of HIF-1αin normal paracancer tissues(Normal), lung squamous cell carcinoma(LUSC), lung adenocarcinoma(LUAD), A549 celland HEB cell. HIF-1α expression was upregulated, and the effects of overexpression of HIF-1α on the proliferation, invasion, and EMT of A549 cells were detected by MTT, cell invasion, and Western blot. HIF-1α expression was down-regulated, ERK and p-ERK protein expressions in A549 cells were detected by Western blot. After THBQactivated the MAPK/ERK pathway, the proliferation, invasion and EMT abilities of A549 cells were analyzed. Cell lines were implanted into nude mice to construct a xenograft model. And the volume and weight of the xenograft tumor were measured. Results HIF-1α expression in non-small cell lung cancer tissues was significantly higher than that in adjacent normal tissues(P<0.05). The expression level of HIF-1α in A549 cells was significantly higher than that in HEB cells(P<0.01). Overexpression of HIF-1α promoted the proliferation and invasion of A549 cells, and the expression level of N-cadherin protein is significantly increased, while that of E-cadherin is significantly decreased. Down-regulation of HIF-1α inhibited the MAPK/ERK pathway in A549 cells and inhibited the proliferation, invasion and EMT of A549 cells. Downregulation of HIF-1α significantly reduced the weight and volume of transplanted tumors in nude mice. Conclusion Silencing HIF-1α inhibited metastasis of non-small cell lung cancer in vivo and in vitro via the MAPK/ERK signaling pathway.

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备注/Memo

备注/Memo:

基金项目: 湖北省卫健委科研项目(WJ2017F008)
通信作者: 陆卫华, Email: 64135789@qq.com

常用功能

更新日期/Last Update: 2021-10-20