Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo

Abstract

Background Recent epidemiologic studies have focused on the potential beneficial effects of regional anesthetics, and the differences in cancer prognosis may be the result of anesthetics on cancer biologic behavior. However, the function and underlying mechanisms of lidocaine in hepatocellular carcinoma both in vitro and in vivo have been poorly studied. Methods Human HepG2 cells were treated with lidocaine. Cell viability, colony formation, cell cycle, and apoptosis were assessed. The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. The antitumor activity of lidocaine in hepatocellular carcinoma with or without cisplatin was investigated with in vitro experiments and also with animal experiments. Results Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle (63.7 ± 1.7% vs. 72.4 ± 3.2%; P = 0.0143) and induced apoptosis (1.7 ± 0.3% vs. 5.0 ± 0.7%; P = 0.0009). Lidocaine may exert these functions by causing an increase in Bax protein and activated caspase-3 and a corresponding decrease in Bcl-2 protein through the extracellular signal-regulated kinase 1/2 and p38 pathways. More importantly, for the first time, xenograft experiments (n = 8 per group) indicated that lidocaine suppressed tumor development (P < 0.0001; lidocaine vs. control) and enhanced the sensitivity of cisplatin (P = 0.0008; lidocaine plus cisplatin vs. cisplatin). Conclusions The authors’ findings suggest that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. Furthermore, combining lidocaine with cisplatin may be a novel treatment option for hepatocellular carcinoma.

Effects of Lidocaine and Ropivacaine on Gastric Cancer Cells Through Down-regulation of ERK1/2 Phosphorylation In Vitro

“…It is supposed that by functional modifications or combination with other drugs, lidocaine might achieve greater anticancer effects. The combination of lidocaine with cisplatin has been proposed as a novel treatment option for hepatocellular carcinoma (19). In this study, we found that lidocaine significantly inhibited the proliferation of AGS and HGC-27 cells at an effective concentration of 10 μM within 72 h with important clinical significance, whilst ropivacaine had an inhibitory effect on gastric cells at 1 mM, which is a much higher dose that can only be achieved by local infiltration clinically.…”

“…breast, lung, liver and thyroid) (15)(16)(17)(18). It has been reported that lidocaine inhibited the growth of HepG2 cells in a dose-dependent and time-dependent manner, arrested cells in the G 0 /G 1 phase of the cell cycle and induced apoptosis (19). Lidocaine at 1 mM was also shown to induce cell-cycle arrest in colon carcinoma cell lines in vitro (20).…”

Cytotoxicity of amide-linked local anesthetics on melanoma cells via inhibition of Ras and RhoA signaling independent of sodium channel blockade

“…Ropivacaine, lidocaine and bupivacaine are amide-linked local anesthetics and act on neuron cells via blocking voltage-gated sodium-channel (VGSC) and subsequent depolarization suppression [8]. They have been shown to exhibit anti-proliferative, antimetastatic and pro-apoptotic potential on cell culture and xenograft mouse models in a variety of cancers [9][10][11][12][13]. In addition, local anesthetics preferentially target cancer stem cells [14].…”

Levobupivacaine inhibits proliferation and promotes apoptosis of breast cancer cells by suppressing the PI3K/Akt/mTOR signalling pathway

“…The growing evidence of local anaesthetics inhibiting cancer cell growth seems promising, though limited [11]. At the tissue level, administration of a certain amount of local anaesthetics topical or local has shown to have a direct inhibitory effect on the action of epidermal growth factor receptor (EGFR) which is a potential target for anti-proliferation in cancer cells [12,13]. Evidence also shows that ropivacaine and lidocaine hinder cancer cells growth, invasion, migration and enhance apoptosis of lung cancer cells [14 -18].…”