[Activation of nuclear factor-κB subunit p50/p65 enhances gefitinib resistance of lung adenocarcinoma H1650 cell line].
Nan Fang Yi Ke Da Xue Xue Bao
; 38(5): 584-590, 2018 May 20.
Article
em Zh
| MEDLINE
| ID: mdl-29891456
ABSTRACT
OBJECTIVE:
To explore the intrinsic connection between activation of classical nuclear factor-κB (NF-κB) pathway and gefitinib resistance in human lung adenocarcinoma H1650 cells.METHODS:
Human lung adenocarcinoma H1650 cells were exposed to gefitinib continuously for 60 days to obtain resistant H1650 cells. The expressions of P-IκBα, P-p50 and P-p65 in the cytoplasm or nuclei were detected using Western blotting in human lung adenocarcinoma HCC827 cells, parental H1650 cells and gefitinib-resistant H1650 cells. The effects of gefitinib alone or in combination with PDTC on the survival rate and expressions of NF-κB P-p50 and P-p65 were compared among the 3 cell lines.RESULTS:
Gefitinib-resistant H1650 cells showed increased cytoplasmic and nuclear P-IκBα expressions. The expressions of P-p50 and P-p65 differed significantly among the 3 cell line, decreasing in the order of resistant H1650 cells, parental H1650 cells, and gefitinib sensitive HCC827 cell lines (P<0.05 or 0.01). Treatment with gefitinib alone resulted in a significantly lower cell inhibition rate in resistant H1650 cells than in the parental H1650 cells (P<0.05) and HCC827 cells (P<0.01). The resistant H1650 cells had a significantly higher expression of P-p50 and P-p65 than other two cell lines (P<0.05). In both the resistant and parental H1650 cells, gefitinib significantly lowered P-p50 and P-p65 expressions (P<0.05 or 0.01), and the combined treatment with gefitinib and PDTC significantly decreased the cell survival rate and further lowered the cytoplasmic and nuclear expressions of P-p50 and P-p65 (P<0.01 or 0.01).CONCLUSION:
The activation of classical NF-κB pathway is a key factor contributing to transformation of the parental H1650 cells into gefitinib-resistant cells. Gefitinib combined with PDTC can inhibit P-IκBα production and NF-κB P-p50 and P-p65 activation to suppress the survival of residual H1650 cells and the generation of gefitinib-resistant cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistencia a Medicamentos Antineoplásicos
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Subunidade p50 de NF-kappa B
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Fator de Transcrição RelA
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Gefitinibe
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Adenocarcinoma de Pulmão
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Antineoplásicos
Limite:
Humans
Idioma:
Zh
Ano de publicação:
2018
Tipo de documento:
Article