Lidocaine alleviates cytotoxicity-resistance in lung cancer A549/DDP cells via down-regulation of miR-21

Abstract

Lidocaine (Lido) is a commonly used local anesthetic, which has been reported in various types of cells. However, the effects of Lido on lung cancer cells remain not understood. The study aimed to investigate the underlying mechanisms of Lido in the cisplatin resistance of A549/DDP cells. Different concentrations of cisplatin (0-320 µM) were used to stimulate A549 and A549/DDP cells, and cell viability and apoptosis were examined. To investigate the effect of Lido on A549/DDP cells, the optimum concentration of Lido was selected to treat A549/DDP cells, and cell viability, apoptosis, migration and invasion were then detected. The relative expression of miR-21 in A549/DDP cells or in Lido-treated A549/DDP cells was analyzed by RT-qPCR. MiR-21 mimic, inhibitor and its control were transfected into A549/DDP cells to explore the regulatory effect of miR-21 on the cisplatin resistance in A549 or A549/DDP cells. The effects of miR-21 on PTEN/PI3K/AKT and PDCD4/JNK pathways were detected by western blot. The cisplatin resistance of A549/DDP cells was higher than that of A549 cells. Lido significantly suppressed cell viability, induced apoptosis, and inhibited cell migration and invasion in A549/DDP cells. Additionally, miR-21 expression in A549/DDP was higher than that in A549 cells, and Lido significantly down-regulated miR-21 expression in A549/DDP cells. MmiR-21 inhibition exhibited the same effects as Lido on the cisplatin resistance of A549/DDP cells. Further, miR-21 suppression regulated PTEN/PI3K/AKT and PDCD4/JNK pathways in A549/DDP cells. These findings indicated that Lido alleviated the cytotoxicity resistance of A549/DDP cells via down-regulation of miR-21.

Keywords: Cisplatin; Lidocaine; Lung cancer; MicroRNA-21; PDCD4/JNK; PTEN/PI3K/AKT.