Lidocaine suppresses the malignant behavior of gastric cancer cells via the c‑Met/c‑Src pathway

Abstract

The present study was designed to investigate the role and mechanism of action behind the action of lidocaine in gastric cancer cells. Lidocaine was tested for its potential role in affecting the viability of cells using Cell Counting Kit-8 (CCK-8) assays. It was found that there was a decreased MKN45 cell viability upon lidocaine treatment in a dose-dependent manner. Phosphorylated c-Met, phosphorylated c-Src, c-Met and c-Src levels were detected using western blotting following lidocaine or hepatocyte growth factor (HGF) intervention. It was found that the phosphorylation levels of c-Met and c-Src were markedly reduced by lidocaine treatment, with this effect being further relieved by the addition of HGF. Subsequently, whether lidocaine repressed the malignant biological properties of gastric cancer cells through the c-Met/c-Src axis was further investigated through the detection of epithelial-mesenchymal transition markers (N-caderin and vimentin), wound healing and transwell assay analysis. In addition, cell apoptosis and the levels of apoptosis-related proteins were determined using TUNEL and western blot assays, respectively. The results demonstrated that the malignant behavior of cells were notably repressed upon lidocaine treatment, but the addition of HGF markedly reversed these effects, indicating that the effects of lidocaine on supressing the malignant behaviour of cells could be mediated through the c-Met/c-Src axis. Subsequently, whether lidocaine affected the sensitivity of cells to cisplatin or 5-FU was analyzed using a CCK-8 assay. Enhanced sensitivity of cells to cisplatin or 5-FU was observed when treated in combination with lidocaine. The present study concluded that the involvement of the c-Met/c-Src pathway in the biological behaviour of MKN45 cells was mediated by lidocaine. Therefore, lidocaine may have the potential to suppress the malignant behaviour and proliferation of gastric cancer cells.

Lidocaine attenuates TMZ resistance and inhibits cell migration by modulating the MET pathway in glioblastoma cells

“…A recent study demonstrated that lidocaine can reduce the mobility of cancer cells and enhance their sensitivity to drug treatment by inhibiting the MET pathway ( 35 ). Given the increased activation of the MET pathway observed in TMZ-resistant GBM cells, it was reasoned that if lidocaine can inhibit the MET pathway, it may potentially suppress the malignant behavior of GBM cells and enhance the therapeutic effect of TMZ.…”

“…In a previous study, lidocaine was revealed to reduce the malignant behavior of gastric cancer cells by inhibiting the c-Met pathway ( 35 ). However, the effect of lidocaine on the HGF/MET pathway in GBM cells remains unclear.…”

“…These findings indicated that lidocaine could potentially serve as a therapeutic option for GBM, although its specific mechanism of action remains largely unknown. Mechanistically, recent research suggests that lidocaine can significantly reduce MET activation ( 35 ). However, whether lidocaine can inhibit the HGF/MET signaling in GBM cells has not been reported yet.…”

Local anaesthetics and chemotherapeutic agents: a systematic review of preclinical evidence of interactions and cancer biology

“… 42 Lidocaine also enhanced the in vitro effect of 5-fluorouracil in a study examining gastric cancer cells, an effect that may be associated with lidocaine-related inhibition of the c-mesenchymal-epithelial transition factor (c-Met)/Proto-oncogene tyrosine-protein kinase Src (c-Src) pathways leading to decreased B-cell lymphoma 2 (Bcl-2) levels and increased levels of Bax and cleaved caspase-3, resulting in apoptosis. 43 …”

Lidocaine Induces Apoptosis in Head and Neck Squamous Cell Carcinoma Through Activation of Bitter Taste Receptor T2R14

“…There are several mechanisms suggested by which lidocaine can induce apoptosis in mammalian cells [102][103][104][105]. However, similarly to studying the effects of lidocaine in HNSCCs, its mechanism(s) of inducing apoptosis following T2R14 activation is/are completely unknown.…”