Effect of perioperative lidocaine on metastasis after sevoflurane or ketamine-xylazine anaesthesia for breast tumour resection in a murine model

Abstract

In this 4T1 murine model of breast cancer, lidocaine decreased pulmonary metastasis when combined with sevoflurane anaesthesia, perhaps via anti-inflammatory and anti-angiogenic effects. It had no such effect in mice given ketamine anaesthesia.

Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration

“…3 And in a murine model of breast cancer metastasis, lidocaine reduced pulmonary metastasis, perhaps by anti-inflammatory or anti-angiogenic mechanisms. 20 Recent studies have shown that, in septic patients, lidocaine can block neutrophil migration by inhibiting cell arrest and transmigration through endothelial cells, affecting G-protein signalling, without modulating expression of adhesion molecules. 21 The present study, focusing on breast tumour cells, shows that lidocaine, at clinical concentrations, can inhibit chemokine-induced cancer cell migration by directly inhibiting the activity of CXCR4.…”

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

“…Although the anticancer efficacies can be confirmed in various cancers, its exact mechanisms/targets remain unclear. As summarized in Table 1 and Figure 2 , the reported targets/mechanisms include MMP-9 ( Piegeler et al, 2015 ), ERK ( Chen et al, 2019 ), TRPV6 ( Jiang et al, 2016 ), and VEGF/VEGFR2 ( Gao et al, 2019 ), as well as the regulation of epigenetics ( Li et al, 2014 ), mi-RNA ( Qu et al, 2018 ; Sui et al, 2019 ; Yang Q. et al, 2019 ), inhibition of metastasis ( D’Agostino et al, 2018 ; Johnson et al, 2018 ; Sun and Sun, 2019 ), inhibition of inflammation ( Freeman et al, 2019 ), impacting mitochondrial metabolism ( Okamoto et al, 2017 ; Gong et al, 2018 ), the regulation of reactive oxygen species (ROS) ( Okamoto et al, 2016 ), etc. Importantly, as an ion channel regulator, lidocaine may exert its anticancer effects via regulation of other channels or membrane potential, such as mitochondrial membrane potential (MMP), which may lead to the decrease of MMP, finally resulting in the mitochondria-related apoptosis ( Li et al, 2014 ; Lu et al, 2016 ; Ye L. et al, 2019 ), providing valuable information for its targets identification.…”

“…Other mechanisms of metastasis inhibition induced by lidocaine in breast cancer cells might be attributed to its anti-inflammatory and anti-angiogenic effects according to a study in 4T1 breast cancer cell line in vitro and in vivo ( Johnson et al, 2018 ). In this study, lidocaine (1.5 mg/kg, intravenous, followed by 25 min infusion at 2 mg/kg/h) showed no growth inhibition in tumor diameter, but it reduced the number of colony counts in lung and liver metastasis significantly via the inhibition of pro-inflammatory and angiogenic cytokine expression as tested in serum in animal models ( Johnson et al, 2018 ). Similar results and mechanisms were also observed in Freeman et al’s study ( Freeman et al, 2019 ), indicating lidocaine’s role in suppressing metastasis of breast cancer via the suppression of pro-inflammation factors.…”

A novel role for lidocaine in COVID-19 patients?

“… 29 In addition, lidocaine has been shown to exhibit a number of anti-inflammatory properties. The ability of lidocaine to inhibit high mobility group box-1 (HMGB-1), 30 and granulocyte colony stimulating factor (G-CSF) merits further research as both HMGB-1 via Toll-like receptor 4 (TLR-4) 31 and G-CSF 32 are key mediators in the initiation of netosis. 33 …”