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Αλέξανδρος Γ. Σφακιανάκης

Monday, March 22, 2021

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

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Exp Ther Med. 2021 May;21(5):424. doi: 10.3892/etm.2021.9868. Epub 2021 Feb 25.

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 hav e the potential to suppress the malignant behaviour and proliferation of gastric cancer cells.

PMID:33747163 | PMC:PMC7967831 | DOI:10.3892/etm.2021.9868

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