The local anesthetic, lidocaine, suppresses the growth of colon cancer SW480 cells by decreasing the voltage-gated sodium channel subunit Nav1.5

Lidocaine is an inhibitor of voltage-gated sodium channels (VGSCs) expressed in excitable cells, such as myocardial cells and sensory neurons, and is used in many clinical situations, including as an anti-arrhythmic and analgesic agent. Clinical studies have suggested that its perioperative application in cancer patients improves their prognosis. Na_v1.5 encoded by the SCN5A gene, which forms the α subunit of VGSC and is a pharmacological target of lidocaine, is expressed in various types of cancer cells. The SCN5A gene is also identified as an upstream regulator of the invasive activity of colon cancer cells, and its aberrant expression correlates with malignancy. Although we previously demonstrated that lidocaine treatment inhibits the growth of cancer cell lines, whether lidocaine induces cell growth suppression through inhibition of Na_v1.5 is still unresolved. Here, we demonstrated that lidocaine induces growth suppression of colon cancer SW480 cells along with a decrease of Na_v1.5. Additionally, lidocaine decreased cyclin D1, a cell cycle promoter, and mutant p53, which has transforming activity in SW480 cells. Since the expression level of Na_v1.5 is associated with the invasiveness of colon cancer, the decrease of Na_v1.5 with the administration of lidocaine has potential as a novel therapeutic strategy for cancer.