PMID- 30881515
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 17
IP  - 4
DP  - 2019 Apr
TI  - Hypoxia-inducible factor-1 signaling pathway influences the sensitivity of HCC827 
      cells to gefitinib.
PG  - 4034-4043
LID - 10.3892/ol.2019.10025 [doi]
AB  - The majority of patients with non-small cell lung cancer (NSCLC) with activating 
      epidermal growth factor receptor (EGFR) mutations inevitably progress in stage 
      despite an initial substantial and rapid response to EGFR-tyrosine kinase 
      inhibitors (EGFR-TKIs). Previous research indicates that hypoxia may be 
      associated with resistance to EGFR-TKIs in EGFR mutation-positive NSCLC. 
      Therefore, the present study regulated the activity of hypoxia-inducible factor-1 
      (HIF-1) signaling pathway to observe if it is able to alter the sensitivity of 
      lung cancer cells to gefitinib. The present study selected 
      3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) and dimethyloxalylglycine 
      (DMOG) as a HIF-1 signaling pathway inhibitor and activator, respectively, on 
      HCC827 cells. Cells were incubated with different treatments for different 
      durations: A blank control, DMOG, gefitinib, or DMOG and gefitinib combined, for 
      36 and 48 h; and then a blank control, YC-1, gefitinib, or YC-1 and gefitinib 
      combined, for 16 and 28 h. A western blot analysis assay was performed to 
      evaluate the protein expression levels of HIF-1alpha and phosphorylated hepatocyte 
      growth factor receptor (p-MET), an MTT assay was used to determine cell 
      proliferation, a colony formation assay was used to investigate the 
      colony-forming ability and a wound healing assay was used to test the cell 
      migration ability. Additionally, Pearson's correlation analysis was used to 
      evaluate the correlation between p-Met and HIF-1alpha expression levels. Finally, it 
      was identified that gefitinib and DMOG combined notably improve the growth and 
      cell migration ability of HCC827 cells, compared with gefitinib alone. When 
      gefitinib and YC-1 were combined, the inhibiting effect on the growth and cell 
      migration ability of HCC827 cells was substantially enhanced, compared with the 
      control cells. Pearson's correlation analysis revealed that the p-Met expression 
      level had a strong positive correlation with HIF-1alpha expression levels. Thus, it 
      was concluded that the HIF-1 signaling pathway influences the sensitivity of 
      HCC827 cells to gefitinib. The positive correlation between p-Met and HIF-1alpha 
      expression levels may be the underlying mechanism of the HIF-1 signaling pathway 
      influencing the sensitivity of HCC827 cells to gefitinib.
FAU - Jin, Qian
AU  - Jin Q
AD  - Department of Respiratory Diseases, First Affiliated Hospital of Zhejiang 
      University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, 
      P.R. China.
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, P.R. China.
FAU - Zhou, Jianying
AU  - Zhou J
AD  - Department of Respiratory Diseases, First Affiliated Hospital of Zhejiang 
      University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, 
      P.R. China.
FAU - Xu, Xianrong
AU  - Xu X
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, P.R. China.
FAU - Huang, Feihua
AU  - Huang F
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, P.R. China.
FAU - Xu, Weihua
AU  - Xu W
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190207
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC6403501
OTO - NOTNLM
OT  - 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
OT  - gefitinib
OT  - hypoxia-inducible factor-1
OT  - oxalylglycine
OT  - phosphorylated hepatocyte growth factor receptor
EDAT- 2019/03/19 06:00
MHDA- 2019/03/19 06:01
PMCR- 2019/02/07
CRDT- 2019/03/19 06:00
PHST- 2018/02/23 00:00 [received]
PHST- 2019/01/11 00:00 [accepted]
PHST- 2019/03/19 06:00 [entrez]
PHST- 2019/03/19 06:00 [pubmed]
PHST- 2019/03/19 06:01 [medline]
PHST- 2019/02/07 00:00 [pmc-release]
AID - OL-0-0-10025 [pii]
AID - 10.3892/ol.2019.10025 [doi]
PST - ppublish
SO  - Oncol Lett. 2019 Apr;17(4):4034-4043. doi: 10.3892/ol.2019.10025. Epub 2019 Feb 
      7.