Lidocaine inhibits the progression of retinoblastoma in vitro and in vivo by modulating the miR520a3p/EGFR axis.
Mol Med Rep
; 20(2): 1333-1342, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31173241
ABSTRACT
Retinoblastoma (RB) is a common malignant tumor in children. Lidocaine is a local anesthetic and antiarrhythmic drug, and has been reported to possess antitumor properties. MicroRNAs (miRs) are a group of endogenous small noncoding RNAs that have important roles in various biological processes via actions on target genes. The aim of the present study was to investigate the effect of lidocaine on retinoblastoma in vitro and in vivo. CCK8 assay and flow cytometry assay were used to measure cell viability and apoptosis. The relationship between miR520a3p and EGFR was predicted and confirmed by TargetScan and dualluciferase reporter assay. For in vivo study, tumor xenograft was performed. In addition, gene and protein expression was detected using reverse transcriptionquantitative polymerase chain reaction and western blotting respectively. In the present study, it was observed that lidocaine inhibited the proliferation and induced the apoptosis of RB cells. miR520a3p was reported to be downregulated in RB tissues and cell lines; treatment with lidocaine increased the expression of miR520a3p in RB cells. The human epidermal growth factor receptor (EGFR) was identified as a direct target of miR520a3p, and its expression was negatively associated with that of miR520a3p. Additionally, EGFR was upregulated in RB tissues and cell lines; treatment with lidocaine decreased the expression of EGFR in RB cells. Furthermore, compared with treatment with lidocaine alone, the combination of transfection with miR520a3p inhibitor and lidocaine treatment significantly decreased the expression of miR520a3p, increased EGFR expression, promoted RB cell proliferation and reduced the apoptosis of cells in vitro, and increased tumor volume and weight in vivo. The results indicated that lidocaine reduced the proliferation and induced the apoptosis of RB cells by decreasing EGFR expression via the upregulation of miR520a3p, suggesting that the miR520a3p/EGFR axis may be a novel therapeutic target in the treatment of RB.
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Base de dados:
MEDLINE
Assunto principal:
Retinoblastoma
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Transdução de Sinais
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Progressão da Doença
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Receptores ErbB
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Lidocaína
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article