Effect of E2F transcription factor 1 on cisplatin-resistant sensitivity of rhinitis carcinoma cells by targeting the ataxia telangiectasia mutated kinase
JIA Ming
BIAN Chao
WU Kaili
Abstract：Objective To explore the role of E2F transcription factor 1(E2F-1)in cisplatin(DDP)-resistant nasopharyngeal carcinoma cells by targeting capillary dilatation ataxia telangiectasia mutated(ATM)kinase and the underlying mechanism.Methods DDP-resistant human nasopharyngeal carcinoma cell lines CNE2(CNE2/DDP)and HNE1(HNE1/DDP),and their parental cells(CNE2 and HNE1)were used to measure their cell viability by MTT assay.Expression levels of E2F1 and ATM in them were detected by the quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)and Western blot.CNE2/DDP and HNE1/DDP were induced with blank control,or transfected with NC-shRNA,E2F1 shRNA-1,E2F1 shRNA-2,overexpression lentivirus of ATM,E2F1 shRNA-1+overexpression lentivirus of ATM,or E2F1 shRNA-2+overexpression lentivirus of ATM.Expression levels of E2F1 and ATM in them were detected by qRT-PCR and Western blot.The mRNA levels of genes associated with drug resistance and cell cycle progression were detected by qRT-PCR.Cell viability,cell cycle and proliferation were examined by MTT assay,flow cytometry and EdU staining,respectively.Results Compared with CNE2,CNE2/DDP had significantly lower DDP inhibition rate,but higher mRNA and protein levels of E2F1 and ATM(P＜0.05).Compared with CNE2/DDP transfected with NC-shRNA,those transfected with E2F1 shRNA-1 or E2F1 shRNA-2 had significantly lower mRNA and protein levels of E2F1 and ATM,expression levels of ABCA2,ABCA5,cyclin E1 and CDK2,cells in S phase and EdU-positive cell number,but higher DDP inhibition rate and cells in G0/G1 phase(P＜0.05).Compared with CNE2/DDP transfected with NC-shRNA,those transfected with overexpression lentivirus of ATM had significantly higher levels of ATM,ABCA2,ABCA5,cyclin E1 and CDK2,cells in S phase and EdU-positive cell number,but lower DDP inhibition rate and cells in G0/G1 phase(P＜0.05),although mRNA and protein levels of E2F1 were comparable(P＞0.05).Compared with CNE2/DDP transfected with overexpression lentivirus of ATM,those transfected with E2F1 shRNA-1+overexpression lentivirus of ATM or E2F1 shRNA-2+overexpression lentivirus of ATM had significantly lower levels of ATM,ABCA2,ABCA5,cyclin E1 and CDK2,cells in S phase and EdU-positive cell number,but higher DDP inhibition rate and cells in G0/G1 phase(P＜0.05).Compared with CNE2/DDP transfected with E2F1 shRNA-1 or E2F1 shRNA-2,those transfected with E2F1 shRNA-1+overexpression lentivirus of ATM or E2F1 shRNA-2+overexpression lentivirus of ATM had significantly higher levels of ATM,ABCA2,ABCA5,cyclin E1 and CDK2,cells in S phase and EdU-positive cell number,but lower DDP inhibition rate and cells in G0/G1 phase(P＜0.05),although mRNA and protein levels of E2F1 were comparable(P＞0.05).Conclusion Knockdown of E2F-1 may reverse DDP resistance in DDP-resistant nasopharyngeal carcinoma cells by modulating ATM,blocking the cell cycle in G1-phase,and reducing the proliferation of DDP-resistant nasopharyngeal carcinoma cells.
Keywords：nasopharyngeal carcinomaE2F transcription factor 1ataxia telangiectasia mutated(ATM)kinasecisplatin resistance
Publication Date：2025-02-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 188-194 )