Ancuta Jurj1, Ciprian Tomuleasa1,2, Tiberiu T. Tat3, Ioana Berindan-Neagoe1, Stefan V. Vesa4, Daniela C. Ionescu5,6
1) Research Center for Functional Genomic, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy;
2) Department of Hematology, and
3) Department of Anesthesia and Intensive Care, Ion Chiricuta Oncology Institute;
4) Department of Pharmacology, Toxicology and Clinical Pharmacology, and
5)Department of Anesthesia and Intensive Care, Iuliu Hatieganu University of Medicine and Pharmacy,
6) Outcome Research Consortium, Cleveland, USA
ABSTRACT Background & Aims: It is now well documented that certain anesthetic techniques may influence long term outcome in cancer patients undergoing surgery. More recently, local anesthetics proved certain antiproliferative effects in cancer cells. In our study, we aimed to investigate if lidocaine has antiproliferative effects in human hepatocarcinoma cells and to identify possible mechanisms of these effects. Methods. We investigated the inhibitory effect of different concentrations of lidocaine on the proliferation of cultured HepG2 human hepatocarcinoma cells and LX2 normal liver fibroblasts. Cells were exposed to nine different concentrations of lidocaine for 72h. MTT assay was used to investigate HepG2 and LX2 proliferation while Western blotting was used for detection of p53 expression level. Results. Our data showed that lidocaine inhibited cell proliferation in a concentration-dependent manner in both HepG2 and LX2. The antiproliferative effects of lidocaine in LX2 were significantly diminished as compared with those in HepG2 (p< 0.001). Similarly, the expression level of p53 was significant decreased in HepG2 lines treated with lidocaine as compared with control and LX2 (p = 0.0241). Conclusions. In clinically relevant concentrations, lidocaine had significant antiproliferative effects on human hepatocarcinoma cells. These effects were time and dose-dependent. One of the possible mechanisms of these effects is by modifying the P53 expression level. The relevance of these findings in clinical practice is limited; clinical impact of these effects on the outcome of patients with hepatocarcinoma undergoing surgery or minimal invasive procedures needs to be demonstrated in future animal models and clinical studies. Key words: lidocaine – hepatocarcinoma cells – antiproliferative.
Abbreviations: DMSO: dimethyl sulfoxide; DNA: deoxyribonucleic acid; EDTA: ethylenediaminetetraacetic acid; EGFR: epidermal growth factor receptor; MTT assay: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay; NK cells: natural killer cells; RCTs: randomized controlled studies; VGSC: voltage gated sodium channels.