Rsf-1 Influences the Sensitivity of Non-Small Cell Lung Cancer to Paclitaxel by Regulating NF-κB Pathway and Its Downstream Proteins.
Cell Physiol Biochem
; 44(6): 2322-2336, 2017.
Article
em En
| MEDLINE
| ID: mdl-29258089
ABSTRACT
BACKGROUND/AIMS:
The therapeutic efficacy of paclitaxel is hampered by chemotherapeutic resistance in non-small cell lung cancer (NSCLC). Rsf-1 enhanced paclitaxel resistance via nuclear factor-κB (NF-κB) in ovarian cancer cells and nasopharyngeal carcinoma. This study assessed the function of Rsf-1 in the modulation of the sensitivity of NSCLC to paclitaxel via the NF-κB pathway.METHODS:
The mRNA and protein levels of the related genes were quantified by RT-PCR and Western blotting. Rsf-1 silencing was achieved with CRISPR/Cas9 gene editing. Cell cycle, migration and proliferation were tested with flow cytometry, transwell test and CCK8 test. Cell apoptosis was analyzed with flow cytometry and quantification of C-capase3. The parameters of the tumors were measured in H460 cell xenograft mice.RESULTS:
Rsf-1 was highly expressed in H460 and H1299 cells. Rsf-1 knockout caused cell arrest at the G1 phase, increased cell apoptosis, and decreased migration and cell proliferation. Rsf-1 knockout increased the inhibition of cell proliferation, the reduction in cell migration and the augment in cell apoptosis in paclitaxel treated H460 and H1299 cells. Rsf-1 knockout further enhanced the paclitaxel-mediated decrease in the volume and weight of the tumors in H460 cell xenograft mice. Helenalin and Rsf-1 knockout decreased the protein levels of p-P65, BcL2, CFLAR, and XIAP; hSNF2H knockout decreased the protein level of NF-κB p-P65 without altering Rsf-1 and p65 protein levels, while Rsf-1 and hSNF2H double knockout decreased the level of NF-κB p-P65, in H1299 and H460 cells.CONCLUSION:
These results demonstrate that Rsf-1 influences the sensitivity of NSCLC to paclitaxel via regulation of the NF-κB pathway and its downstream genes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Transativadores
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NF-kappa B
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Paclitaxel
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Carcinoma Pulmonar de Células não Pequenas
/
Resistencia a Medicamentos Antineoplásicos
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Neoplasias Pulmonares
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Antineoplásicos Fitogênicos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article