Lidocaine inhibits the proliferation and metastasis of epithelial ovarian cancer through the Wnt/β-catenin pathway

Abstract

Background: Lidocaine, an amide local anesthetic, has recently been found to have anticancer action in various cancer cells. However, the role of lidocaine in epithelial ovarian cancer (EOC) remains largely unknown. In the present study, we investigated how lidocaine regulates the progression of EOC.Methods: Real-time polymerase chain reaction was used to examine the expression of Snail, Wnt, β-catenin, E-cadherin, vimentin, matrix metalloproteinase (MMP)-7, MMP-9, and vascular endothelial growth factor in lidocaine-treated cells. Cell proliferation assays, cell apoptosis assays, and cell migration assays were employed to verify the function of lidocaine in EOC cells. Cell proliferation and cell migration assays were employed to verify the function of Wnt/β-catenin signaling in lidocaine-treated EOC cells together with Wnt-overexpressing plasmids or inhibitor NVP-XAV939.Results: Lidocaine could inhibit proliferation, migration, and invasion, and induce apoptosis in ovarian cancer cells lines in a dose-dependent manner. Wnt/β-catenin signaling was involved in the suppression of epithelial-mesenchymal transition progression of ovarian cancer cells, which resulted in the downregulation of Snail and vimentin, as well as the upregulation of E-cadherin. Furthermore, overexpressed Wnt could reverse the carcinostatic effect of lidocaine, while Wnt inhibitor XAV-939 synergistically enhanced the antitumor effect of lidocaine.Conclusions: Mechanistically, lidocaine could inhibit the proliferation and metastasis of EOC by the Wnt/ β-catenin pathway to regulate the progression of EOC.

Trial watch: local anesthetics in cancer therapy

“… 17–19 Lidocaine was also found to inhibit the WNT/beta-catenin pathway, thus blocking epithelial-mesenchymal transition and impairing the progression of ovarian cancer. 20 Bupivacaine reportedly interferes with gastric cell migration by blocking the RHO-A/RHO-associated protein kinase (ROCK)/myosin light chain (MLC) pathway, and ropivacaine reduces the migration of esophageal and thyroid cancer cells by inhibiting the RAS-related C3 botulinum toxin substrate 1/c-JUN N-terminal kinase/paxillin/focal adhesion kinase (RAC1/JNK/paxillin/FAK) pathway and integrin-alpha-2 expression, respectively. 21–23 Moreover, ropivacaine may interact with integrin-beta1, which is involved in tumorigenesis, ultimately inducing apoptosis.…”

Drug Repurposing: The Mechanisms and Signaling Pathways of Anti-Cancer Effects of Anesthetics

“…This in vitro study suggests that bupivacaine may possess a direct anti-cancer effect by activating apoptotic pathways against ovarian and prostate cancer. Sun et al have also reported that the inhibitory effects of lidocaine on cell proliferation and metastasis are mediated by the Wnt/β-catenin pathway of ovarian cancer cells [ 72 ]. Similar results are also found in HCC, where lidocaine treatment causes apoptosis through the activation of pro-apoptotic protein Bax, caspase cascade, and a corresponding decrease in anti-apoptotic protein Bcl-2 through the extracellular signal-regulated kinase (ERK) 1/2 and p38 pathways.…”

β‐Catenin‐treated peptides effectively inhibit the proliferation of colorectal cancer

“…β‐Catenin is a key protein that promotes the development of human cancer. For example, β‐catenin downregulation could contribute to cisplatin‐based chemotherapy for bladder cancer, 3 and its inhibition could contribute to the suppression of proliferation and metastasis of ovarian cancer cells 4 . β‐Catenin is not only a component of the Wnt/Wg pathway 5 but also promotes cell adhesion 6 .…”

“…For example, β-catenin downregulation could contribute to cisplatin-based chemotherapy for bladder cancer, 3 and its inhibition could contribute to the suppression of proliferation and metastasis of ovarian cancer cells. 4 β-Catenin is not only a component of the Wnt/Wg pathway 5 but also promotes cell adhesion. 6 Similarly, the Wnt/β-catenin pathway plays an important role in CRC development.…”