In vitro antitumor effects and apoptosis-related mechanisms of lidocaine in renal cell carcinoma A498 cells.

[OBJECTIVE] The aim of this study is to assess the antitumor properties and associated molecular mechanisms of lidocaine on renal cell carcinoma (RCC) A498 cells under in vitro conditions.

[METHODS] RCC A498 cells were exposed to varying concentrations of lidocaine (0, 0.1, 0.5, 1, 2, and 5 mM) for 24, 48, and 72 h. Cell viability was assessed using the Cell Counting Kit-8 assay to identify effective concentrations. Based on these results, further experiments were conducted using lidocaine at 0, 0.1, 0.5, and 1 mM for 48 h. Apoptotic changes were evaluated using a double-staining apoptosis detection kit, followed by analysis through flow cytometry. Cell migration was assessed using a 24-h Transwell migration assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure mRNA expression levels CASP3, CASP8, CASP9, and ACTB. Protein expression levels of BCL2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, Caspase-8, and Caspase-9 were examined through immunoblotting following treatment with 1 mM lidocaine for 48 h.

[RESULTS] Lidocaine inhibited A498 cell viability in a dose- and time-dependent manner. A reduction in migratory activity was observed with increasing lidocaine concentrations. Flow cytometric analysis demonstrated significantly elevated apoptosis rates at 0.1, 0.5, and 1 mM lidocaine compared to untreated controls (p < 0.05). qRT-PCR analysis demonstrated upregulation of CASP3, CASP8, and CASP9 transcripts. Western blot results confirmed increased protein expression of Bax, Caspase-3, and Caspase-9, along with decreased Bcl-2 levels.

[CONCLUSION] Lidocaine exhibited antitumor activity against RCC A498 cells in vitro by suppressing proliferation, inhibiting migration, and promoting apoptosis via activation of caspase-dependent pathways.