PMID- 34345296
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210806
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Print)
IS  - 1792-1074 (Linking)
VI  - 22
IP  - 3
DP  - 2021 Sep
TI  - Angiogenic activities are increased via upregulation of HIF-1alpha expression in 
      gefitinib-resistant non-small cell lung carcinoma cells.
PG  - 671
LID - 10.3892/ol.2021.12932 [doi]
LID - 671
AB  - 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-1alpha 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-1alpha 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-1alpha 
      and angiogenesis within the tumors. Furthermore, inhibition of HIF-1alpha suppressed 
      resistance to gefitinib, whereas overexpression of HIF-1alpha increased resistance to 
      gefitinib. The results from the present study provides evidence that HIF-1alpha was 
      associated with the acquisition of resistance to gefitinib and suggested that 
      inhibiting HIF-1alpha alleviated gefitinib resistance in NSCLC cell lines.
CI  - Copyright: (c) Cha et al.
FAU - Cha, Jeong Eun
AU  - Cha JE
AD  - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 
      02447, Republic of Korea.
FAU - Bae, Woom-Yee
AU  - Bae WY
AD  - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 
      02447, Republic of Korea.
AD  - Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee 
      University, Seoul 02447, Republic of Korea.
FAU - Choi, Jae-Sun
AU  - Choi JS
AD  - Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee 
      University, Seoul 02447, Republic of Korea.
AD  - Medical Science Research Institute, Kyung Hee University, Seoul 02447, Republic 
      of Korea.
FAU - Lee, Seung Hyeun
AU  - Lee SH
AD  - Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal 
      Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Republic of 
      Korea.
FAU - Jeong, Joo-Won
AU  - Jeong JW
AD  - Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 
      02447, Republic of Korea.
AD  - Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee 
      University, Seoul 02447, Republic of Korea.
LA  - eng
PT  - Journal Article
DEP - 20210718
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC8323004
OTO - NOTNLM
OT  - EGFR-TKIs
OT  - HIF-1alpha
OT  - NSCLC
OT  - angiogenesis
OT  - gefitinib
COIS- The authors declare that they have no competing interests.
EDAT- 2021/08/05 06:00
MHDA- 2021/08/05 06:01
PMCR- 2021/07/18
CRDT- 2021/08/04 07:06
PHST- 2021/03/11 00:00 [received]
PHST- 2021/06/30 00:00 [accepted]
PHST- 2021/08/04 07:06 [entrez]
PHST- 2021/08/05 06:00 [pubmed]
PHST- 2021/08/05 06:01 [medline]
PHST- 2021/07/18 00:00 [pmc-release]
AID - OL-0-0-12932 [pii]
AID - 10.3892/ol.2021.12932 [doi]
PST - ppublish
SO  - Oncol Lett. 2021 Sep;22(3):671. doi: 10.3892/ol.2021.12932. Epub 2021 Jul 18.