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Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells

  • Authors:
    • Jeong Eun Cha
    • Woom-Yee Bae
    • Jae-Sun Choi
    • Seung Hyeun Lee
    • Joo-Won Jeong
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea, Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
    Copyright: © Cha et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 671
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    Published online on: July 18, 2021
       https://doi.org/10.3892/ol.2021.12932
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Abstract

Epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitors (TKIs) have been used to treat patients with non‑small cell lung cancer (NSCLC) and activating EGFR mutations; however, the emergence of secondary mutations in EGFR or the acquisition of resistance to EGFR‑TKIs can develop and is involved in clinical failure. Since angiogenesis is associated with tumor progression and the blockade of antitumor drugs, inhibition of angiogenesis could be a rational strategy for developing anticancer drugs combined with EGFR‑TKIs to treat patients with NSCLC. The signaling pathway mediated by hypoxia‑inducible factor‑1 (HIF‑1) is essential for tumor angiogenesis. The present study aimed to identify the dependence of gefitinib resistance on HIF‑1α activity using angiogenesis assays, western blot analysis, colony formation assay, xenograft tumor mouse model and immunohistochemical analysis of tumor tissues. In the NSCLC cell lines, HIF‑1α protein expression levels and hypoxia‑induced angiogenic activities were found to be increased. In a xenograft mouse tumor model, tumor tissues derived from gefitinib‑resistant PC9 cells showed increased protein expression of HIF‑1α and angiogenesis within the tumors. Furthermore, inhibition of HIF‑1α suppressed resistance to gefitinib, whereas overexpression of HIF‑1α increased resistance to gefitinib. The results from the present study provides evidence that HIF‑1α was associated with the acquisition of resistance to gefitinib and suggested that inhibiting HIF‑1α alleviated gefitinib resistance in NSCLC cell lines.
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Cha JE, Bae W, Choi J, Lee SH and Jeong J: Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells. Oncol Lett 22: 671, 2021.
APA
Cha, J.E., Bae, W., Choi, J., Lee, S.H., & Jeong, J. (2021). Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells. Oncology Letters, 22, 671. https://doi.org/10.3892/ol.2021.12932
MLA
Cha, J. E., Bae, W., Choi, J., Lee, S. H., Jeong, J."Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells". Oncology Letters 22.3 (2021): 671.
Chicago
Cha, J. E., Bae, W., Choi, J., Lee, S. H., Jeong, J."Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells". Oncology Letters 22, no. 3 (2021): 671. https://doi.org/10.3892/ol.2021.12932
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Spandidos Publications style
Cha JE, Bae W, Choi J, Lee SH and Jeong J: Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells. Oncol Lett 22: 671, 2021.
APA
Cha, J.E., Bae, W., Choi, J., Lee, S.H., & Jeong, J. (2021). Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells. Oncology Letters, 22, 671. https://doi.org/10.3892/ol.2021.12932
MLA
Cha, J. E., Bae, W., Choi, J., Lee, S. H., Jeong, J."Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells". Oncology Letters 22.3 (2021): 671.
Chicago
Cha, J. E., Bae, W., Choi, J., Lee, S. H., Jeong, J."Angiogenic activities are increased via upregulation of HIF‑1α expression in gefitinib‑resistant non‑small cell lung carcinoma cells". Oncology Letters 22, no. 3 (2021): 671. https://doi.org/10.3892/ol.2021.12932
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