Lidocaine inhibits the progression of retinoblastoma in�vitro and in�vivo by modulating the miR‑520a‑3p/EGFR axis

Abstract

Retinoblastoma (RB) is a common malignant tumor in children. Lidocaine is a local anesthetic and anti-arrhythmic drug, and has been reported to possess anti-tumor 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 . CCK-8 assay and flow cytometry assay were used to measure cell viability and apoptosis. The relationship between miR-520a-3p and EGFR was predicted and confirmed by TargetScan and dual-luciferase reporter assay. For in vivo study, tumor xenograft was performed. In addition, gene and protein expression was detected using reverse transcription-quantitative 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. miR-520a-3p was reported to be downregulated in RB tissues and cell lines; treatment with lidocaine increased the expression of miR-520a-3p in RB cells. The human epidermal growth factor receptor (EGFR) was identified as a direct target of miR-520a-3p, and its expression was negatively associated with that of miR-520a-3p. 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 miR-520a-3p inhibitor and lidocaine treatment significantly decreased the expression of miR-520a-3p, 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 miR-520a-3p, suggesting that the miR-520a-3p/EGFR axis may be a novel therapeutic target in the treatment of RB.

microRNA -378a-3p Restrains the Proliferation of Retinoblastoma Cells but Promotes Apoptosis of Retinoblastoma Cells via Inhibition of FOXG1

“…The prepared Y79 cell suspension (1 mL) that was prepared was subcutaneously injected into left armpit of the nude mice with a syringe. 19 , 20 …”

“…The prepared Y79 cell suspension (1 mL) that was prepared was subcutaneously injected into left armpit of the nude mice with a syringe. 19,20 When the tumor tissue size reached 50 mm 3 , the nude mice were injected with miR-378a-3p agomir or NC agomir at a dosage of 10 nmol/mouse once every 5 days for a total of 5 weeks, 6 mice per treatment group. Five weeks later, the mice were euthanized, followed by the extraction of subcutaneous xenotransplanted tumors with the tumor weight recorded.…”

Anesthetics or anesthetic techniques and cancer surgical outcomes: a possible link

“…In a dose-dependent manner , lidocaine demonstrated anti-tumor activity by inhibiting the PI3K/AKT/mTOR signaling pathway [ 71 ]. Lidocaine (50, 100, 500 or 1000 μM) has been seen to also inhibit the growth of retinoblastomas by modulation of the miR-520a-3p/EGFR axis [ 72 ] and human gastric cancers by alteration of the MAPK pathway [ 73 ].…”

<p>Anesthesia Options and the Recurrence of Cancer: What We Know so Far?</p>

“…[41][42][43] Lidocaine also induces modulation of microRNAs. [44][45][46][47] Treatment of lung cancer cells with 8 mM of lidocaine significantly increased the expression of miR-539, which then induced the downregulation of the epidermal growth factor receptor (EGFR) and suppressed migration and invasion. 45 The intravenous injection of lidocaine (1.5 mg/kg) to mice bearing retinoblastoma caused significant tumor reduction by inducing the expression of miR520a-3p and inhibiting EGFR.…”

“…45 The intravenous injection of lidocaine (1.5 mg/kg) to mice bearing retinoblastoma caused significant tumor reduction by inducing the expression of miR520a-3p and inhibiting EGFR. 46 MicroRNAs are also involved in chemo-resistance. Lidocaine, in vitro, inhibited the expression of miR-21 and sensitized chemo-resistant lung cancer cells to cisplatin.…”