PMID- 31933796
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200117
IS  - 1936-2625 (Electronic)
IS  - 1936-2625 (Linking)
VI  - 12
IP  - 11
DP  - 2019
TI  - Decitabine reverses gefitinib resistance in PC9 lung adenocarcinoma cells by 
      demethylation of RASSF1A and GADD45beta promoter.
PG  - 4002-4010
AB  - The acquired resistance to epidermal growth factor receptor tyrosine kinase 
      inhibitor (EGFR-TKI) is the major reason for the failure of target therapy in 
      advanced non small cell lung cancer (NSCLC) patients, the mechanism of which has 
      not been fully elucidated yet. The present study aimed to investigate the 
      different DNA methylation profile before and after acquired EGFR-TKI resistance, 
      and explore the influence of the DNA demethylater, decitabine, on EGFR-TKI 
      resistance. The DNA methylation chip was used to screen the genes whose DNA 
      methylation status were changed in the EGFR-TKI sensitive human NSCLC cell line 
      PC9, and the induced EGFR-TKI resistant NSCLC cell line PC9/GR (harboring T790M 
      mutation). According to the results and literature reports, the tumor suppressor 
      genes, RASSF1A and GADD45beta were selected for further research. Methylation 
      specific PCR (MSP) and western blot further confirmed that the promoters of these 
      two genes were methylated, and the protein expressions were significantly 
      inhibited in PC9/GR cells. Additionally, decitabine, the DNA methyl transferase 
      inhibitor, could reverse the methylation status of RASSF1A and GADD45beta promoters, 
      elevate protein expression, and partially restore the sensitivity of PC9/GR cells 
      to EGFR-TKI. To conclude, our results suggested that the DNA methylation of 
      RASSF1 and GADD45beta may play a role in EGFR-TKI resistance, and epigenetic 
      intervention might be an effective strategy to reverse EGFR-TKI resistance, 
      suggesting further study.
CI  - IJCEP Copyright (c) 2019.
FAU - Hou, Tao
AU  - Hou T
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Ma, Jin'an
AU  - Ma J
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Hu, Chunhong
AU  - Hu C
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Zou, Fangwen
AU  - Zou F
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Jiang, Shun
AU  - Jiang S
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Wang, Yapeng
AU  - Wang Y
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Han, Chen
AU  - Han C
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Department of Oncology, Second Xiangya Hospital, Central South University 
      Changsha, Hunan, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20191101
PL  - United States
TA  - Int J Clin Exp Pathol
JT  - International journal of clinical and experimental pathology
JID - 101480565
PMC - PMC6949799
OTO - NOTNLM
OT  - Lung adenocarcinoma
OT  - decitabine
OT  - gefitinib resistance
OT  - methylation
COIS- None.
EDAT- 2020/01/15 06:00
MHDA- 2020/01/15 06:01
PMCR- 2019/11/01
CRDT- 2020/01/15 06:00
PHST- 2018/11/06 00:00 [received]
PHST- 2018/12/23 00:00 [accepted]
PHST- 2020/01/15 06:00 [entrez]
PHST- 2020/01/15 06:00 [pubmed]
PHST- 2020/01/15 06:01 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
PST - epublish
SO  - Int J Clin Exp Pathol. 2019 Nov 1;12(11):4002-4010. eCollection 2019.