PMID- 38163975
OWN - NLM
STAT- MEDLINE
DCOM- 20240103
LR  - 20240108
IS  - 1999-6187 (Electronic)
IS  - 1009-3419 (Print)
IS  - 1009-3419 (Linking)
VI  - 26
IP  - 12
DP  - 2024 Jan 2
TI  - [Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells 
to 
      Osimertinib by Regulating Methylation of DUSP1].
PG  - 881-888
LID - 10.3779/j.issn.1009-3419.2023.106.24 [doi]
AB  - BACKGROUND: Drug resistance is the main cause of high mortality of lung cancer. 
      This study was conducted to investigate the effect of folic acid (FA) on the 
      resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by 
      regulating the methylation of dual specificity phosphatase 1 (DUSP1). METHODS: 
      The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of 
      OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control 
      group, OSM group (5 mumol/L OSM), FA group (600 nmol/L FA), methylation inhibitor 
      decitabine (DAC) group (10 mumol/L DAC), FA+OSM group (600 nmol/L FA+5 mumol/L 
      OSM), and FA+OSM+DAC group (600 nmol/L FA+5 mumol/L OSM+10 mumol/L DAC). CCK-8 
      method was applied to detect cell proliferation ability. Scratch test was applied 
      to test the ability of cell migration. Transwell assay was applied to detect cell 
      invasion ability. Flow cytometry was applied to measure and analyze the apoptosis 
      rate of cells in each group. Real-time fluorescence quantitative polymerase chain 
      reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 
      mRNA in cells. Methylation specific PCR (MSP) was applied to detect the 
      methylation status of the DUSP1 promoter region in each group. Western blot was 
      applied to analyze the expression levels of DUSP1 protein and key proteins in the 
      DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in 
      each group. RESULTS: Compared with the Control group, the cell OD450 values (48 
      h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 
      in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the 
      methylation level of DUSP1, the expression of p38 MAPK protein, and the 
      phosphorylation level of extracellular regulated protein kinases (ERK) were 
      obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing 
      rate, number of cell invasions, and expression of DUSP1 in the DAC group were 
      obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK 
      protein, the phosphorylation level of ERK, and the methylation level of DUSP1 
      were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 
      values (48, 72 h), scratch healing rate, number of cell invasions, and expression 
      of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis 
      rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the 
      phosphorylation level of ERK were obviously increased (P<0.05). Compared with the 
      FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of 
      cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously 
      increased; the apoptosis rate, the methylation level of DUSP1, the expression of 
      p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced 
      (P<0.05). CONCLUSIONS: FA may inhibit DUSP1 expression by enhancing DUSP1 
      methylation, regulate downstream MAPK signal pathway, then promote apoptosis, 
      inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in 
      NSCLC cells.
FAU - He, Wenjuan
AU  - He W
AD  - Department of Pharmacy, Wuhan No. 4 Hospital, Wuhan 430030, China.
FAU - Liu, Li
AU  - Liu L
AD  - Department of Pharmacy, Wuhan No. 4 Hospital, Wuhan 430030, China.
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhongguo Fei Ai Za Zhi
JT  - Zhongguo fei ai za zhi = Chinese journal of lung cancer
JID - 101126433
RN  - 3C06JJ0Z2O (osimertinib)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.48 (DUSP1 protein, human)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics
MH  - *Lung Neoplasms/drug therapy/genetics
MH  - Dual Specificity Phosphatase 1/genetics/metabolism/pharmacology
MH  - Cell Proliferation
MH  - p38 Mitogen-Activated Protein Kinases/metabolism/pharmacology
MH  - Methylation
MH  - Apoptosis
MH  - Cell Line, Tumor
PMC - PMC10767649
OTO - NOTNLM
OT  - Dual specificity phosphatase 1
OT  - Folic acid
OT  - Lung neoplasms
OT  - Methylation
OT  - Osimertinib
OT  - Resistance
EDAT- 2024/01/02 11:44
MHDA- 2024/01/03 09:42
PMCR- 2023/12/20
CRDT- 2024/01/02 02:23
PHST- 2024/01/03 09:42 [medline]
PHST- 2024/01/02 11:44 [pubmed]
PHST- 2024/01/02 02:23 [entrez]
PHST- 2023/12/20 00:00 [pmc-release]
AID - 10.3779/j.issn.1009-3419.2023.106.24 [doi]
PST - ppublish
SO  - Zhongguo Fei Ai Za Zhi. 2024 Jan 2;26(12):881-888. doi: 
      10.3779/j.issn.1009-3419.2023.106.24.