Lidocaine Inhibited Migration of Non-Small-Cell Lung Cancer A549 Cells via the CXCR4 Regulation

Abstract BackgroundLidocaineis a local anestheticthat wildly used in surgical treatment and postoperative medical care for lung cancers.We hypothesized thatlidocaine at clinical plasma concentrationcan inhibit CXCL12/CXCR4 axis regulated cytoskeletal remodeling thereby decrease migration ofNon-small-cell lung cancers (NSLC) cells. MethodsWe determined the effect of lidocaine at clinical plasma concentration on CXCL12-induced cell viability, apoptosis, cell death, monolayer cell wound healing rate, individual cell migration indicators, expression of CXCR4, CD44, and ICAM-1, intracellular Ca2+level, and filamentous actin level alteration of NSLC cells A549 and CXCR4-knocked down A549 cells using CCK-8, Bcl-2 ELISA, Cell death ELISA, wound healing assay, chemotaxis assay, western blotting, QPCR, Fura-2-based intracellular Ca2+assay, and Fluorescein Phalloidin staining respectively.ResultsLidocaine did not affect cell viability, apoptosis, and cell death but inhibited CXCL12-induced migration,intracellular Ca2+ releasing, and filamentous actin increase. Lidocaine decreased expression of CXCR4, increased CD44, but had no effect on ICAM-1. CXCL12induced the increase of CD44 and ICAM-1 but did not affect CD44 in the presence of lidocaine.The knockdown of CXCR4 eliminated all the effects of lidocaine.ConclusionLidocaine at clinical plasma concentrations inhibited CXCL12-induced CXCR4 activation, thereby reduced the intracellular Ca2+-dependent cytoskeleton remodeling, resulting in slower migration of A549 cells.