Lidocaine could promote the cuproptosis through up-regulating the long noncoding RNA DNMBP-AS1 in laryngeal cancer

Abstract

AbstractBackground:Lidocaine is a traditional local anesthetic, which has been reported to trigger apoptosis through the mitochondrial pathway, independent of death receptor signaling. Cuproptosis is a copper triggered mitochondrial cell death mode. In this study, we explored the biological effects of lidocaine on laryngeal cancer and studied the relevant mechanisms of cuproptosisMethods:quantitative RT-PCR weas used to measure the expression level of long noncoding RNA (IncRNA) DNMBP-AS1. DNMBP-AS1 siRNA (si-DNMBP-AS1) were transfected into Hep-2 cells to verify the roles of DNMBP-AS1 in cuproptosis. 24 hours treatment with 20 nM elesclomol and 2 µM CuCl2 was performed to promote the occurrence of Cuproptosis. Cell proliferation and apoptosis assays ware utilized to analyze biological effect of lidocaine on Hep-2 cells.Results:DNMBP-AS1 was significantly upregulated during cuproptosis in Hep-2 cells. The si-DNMBP-AS1 significantly increased the cell viability, and suppress the cuproptosis. Lidocaine was cytotoxic to the Hep-2 cells in a dose- and time-dependent manner. Exposure to 10 μM of lidocaine for 24 hours did not reduce the viability, but significantly increased the expression of DNMBP-AS1, and promote the cuproptosis. Anymore, si-DNMBP-AS1 reverse the pro-cuproptosis function of lidocaine.Conclusions:lidocaine was cytotoxic to human laryngeal cancer cells in a time- and dose-dependent manner, promoted the cuproptosis through up-regulating DNMBP-AS1. The results of this study offer initial optimism that lidocaine can be used in an adjuvant or neoadjuvant fashion in laryngeal cancer treatment.