PMID- 33763171
OWN - NLM
STAT- MEDLINE
DCOM- 20210519
LR  - 20220421
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2021
DP  - 2021
TI  - HIF-1 Inhibitor YC-1 Reverses the Acquired Resistance of EGFR-Mutant HCC827 Cell 
      Line with MET Amplification to Gefitinib.
PG  - 6633867
LID - 10.1155/2021/6633867 [doi]
LID - 6633867
AB  - BACKGROUND: Acquired resistance occurred in the majority of nonsmall cell lung 
      cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine 
      kinase inhibitors (EGFR-TKIs) therapy, and this may be related to the activation 
      of the HIF-1 pathway. Therefore, we examined the influence of the 
      hypoxia-inducible factor-1 (HIF-1) pathway inhibition on the sensitivity of 
      HCC827 gefitinib-resistant (HCC827 GR) cells with MET amplification to gefitinib. 
      METHODS: We established HCC827 GR cell line with MET amplification and set four 
      groups with different treatment. An MTT assay, a colony formation analysis, and a 
      wound healing assay were performed to determine the sensitivity change of HCC827 
      GR cells after different treatments. HIF-1alpha, p-EGFR, and p-Met levels were 
      detected with western blot. Correlations among HIF-1alpha, p-EGFR, and p-Met levels 
      of HCC827 GR cells with different treatments were analyzed with Pearson's 
      correlation analysis. RESULTS: HIF-1 inhibitor YC-1 enhanced the sensitivity of 
      HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1alpha level, while 
      there was no correlation between p-Met level and p-EGFR level. CONCLUSION: HIF-1 
      inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to 
      gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the 
      mechanisms.
CI  - Copyright (c) 2021 Qian Jin et al.
FAU - Jin, Qian
AU  - Jin Q
AUID- ORCID: 0000-0002-9254-0359
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, China.
FAU - Zheng, Jisheng
AU  - Zheng J
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, China.
FAU - Chen, Ming
AU  - Chen M
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, China.
FAU - Jiang, Na
AU  - Jiang N
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, China.
FAU - Xu, Xianrong
AU  - Xu X
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, China.
FAU - Huang, Feihua
AU  - Huang F
AUID- ORCID: 0000-0002-5853-772X
AD  - Department of Respiratory Medicine, Tongde Hospital of Zhejiang Province, 
      Hangzhou, Zhejiang 310012, China.
LA  - eng
PT  - Journal Article
DEP - 20210303
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Indazoles)
RN  - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Down-Regulation/drug effects
MH  - Drug Resistance, Neoplasm/drug effects/*genetics
MH  - ErbB Receptors/genetics
MH  - Gefitinib/*pharmacology
MH  - *Gene Amplification
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors/metabolism
MH  - Indazoles/*pharmacology
MH  - Mutation/*genetics
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-met/*genetics
MH  - Tumor Stem Cell Assay
MH  - Wound Healing/drug effects
PMC - PMC7946473
COIS- The authors declare that they have no competing interests.
EDAT- 2021/03/26 06:00
MHDA- 2021/05/20 06:00
PMCR- 2021/03/03
CRDT- 2021/03/25 06:28
PHST- 2020/10/17 00:00 [received]
PHST- 2021/01/30 00:00 [revised]
PHST- 2021/02/14 00:00 [accepted]
PHST- 2021/03/25 06:28 [entrez]
PHST- 2021/03/26 06:00 [pubmed]
PHST- 2021/05/20 06:00 [medline]
PHST- 2021/03/03 00:00 [pmc-release]
AID - 10.1155/2021/6633867 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2021 Mar 3;2021:6633867. doi: 10.1155/2021/6633867. 
      eCollection 2021.