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Chinese Journal of Lung Diseases(Electronic Edition) ›› 2021, Vol. 14 ›› Issue (05): 573-578. doi: 10.3877/cma.j.issn.1674-6902.2021.05.006

• Original Article • Previous Articles     Next Articles

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

Zhiguo Yu1, Bo Gong1, Weihua Lu1,(), Minfang Li2   

  1. 1. Emergency Department, Central Theater Command General Hospital, Wuhan 430014, China
    2. Oncology Department, Central Theater Command General Hospital, Wuhan 430014, China
  • Received:2021-03-11 Online:2021-10-25 Published:2021-11-12
  • Contact: Weihua Lu

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.

Key words: HIF-1α, MAPK/ERK, Metastasis, Non-small cell lung cancer

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