Lidocaine exerts anticancer activity in bladder cancer by targeting isoprenylcysteine carboxylmethyltransferase (ICMT)

Background: Bladder cancer is one of the most common malignant tumors among humans and has a high mortality. Clinically, lidocaine is the most commonly used local anesthetic, which can inhibit the proliferation of bladder cancer cells; however, its downstream specific molecular mechanisms are unclear. Methods: The SwissTarget and TargetNet databases were used to analyze the target of lidocaine. The online public cancer transcriptome database UALCAN was used to analyze the up-regulated genes in The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) data collection, and the intersection of the 2 was used to obtain the core target. The only target, isoprenylcysteine carboxylmethyltransferase (ICMT), was obtained by combining the correlation between the target and the clinical information of bladder cancer and the Kaplan-Meier (K-M) survival curve. Then, UMUC3 and T24 cells were selected as research vectors in vitro. Cell proliferation, cell cycle, and apoptosis were detected by cell counting kit-8, colony formation, flow cytometry, and western blotting. Results: Network pharmacology analysis showed that ICMT might be one of the targets of lidocaine, and the expression level of ICMT was closely related to the clinical phenotype of bladder cancer. Lidocaine treatment (4 and 8 mM) significantly inhibited the proliferation of UMUC3 and T24 cells, promoted apoptosis, and significantly inhibited the mass and volume of xenograft tumors. In vitro experiments showed that ICMT promoted the proliferation of UMUC3 and T24 cells. Lidocaine inhibited the expression of ICMT in UMUC3 and T24 cells in a concentration and time-dependent manner, and inhibited cell proliferation by down-regulating ICMT expression. Conclusions: Lidocaine exerts anti-tumor effect by down-regulating the expression of ICMT in bladder cancer.