Lidocaine inhibits proliferation and metastasis of lung cancer cell via regulation of miR-539/EGFR axis

Abstract

Background: Despite the medical uses of lidocaine has been well-characterized, the study of lidocaine's pharmacological function other the anaesthetic effect was never stopped. This study designed to reveal the effect of lidocaine on the growth and metastasis of lung cancer in vitro. Methods: A549 and NCI-H1299 cells were treated by lidocaine for 24 h. miR-539 expression in cell was silenced by transfection with the specific inhibitor. The changes in cell growth and metastasis were determined using CCK-8 assay and western blot. Luciferase activity assay was performed to assay if EGFR was a target of miR-539. Western blot was used to test the activation of EGFR downstream signalling. Results: Lidocaine suppressed the viability, migration, and invasion of A549 and NCI-H1299 cells while induced apoptotic death. Lidocaine elevated the expression of miR-539. The anti-tumour properties of lidocaine towards A549 and NCI-H1299 cells were partially attenuated when miR-539 was silenced. EGFR was a target of miR-539. Lidocaine repressed the activation of ERK and PI3K/AKT pathways also via regulating miR-539. Conclusion: The anti-growth and anti-metastatic effects of lidocaine towards lung cancer cells. The anti-tumour properties of lidocaine may be partial via up-regulation of miR-539, which blocked EGFR signalling by directly binding with EGFR.

Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides’ immunogenicity

“…Cells were lysed, and total protein was resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to reinforced nitrocellulose according to 56 . The membranes were blocked with 5% non-fat dry milk in PBS/0.1% Tween-20 or with 3% BSA in PBS/0.1% Tween-20, and incubated with anti-MMP-9 monoclonal antibodies 57 followed by enhanced chemiluminescence detection (ECL, Amersham, Alington Heights, IL). The membranes were rehydrated in PBS/Tween-20, stripped with 100 mM mercaptoethanol and 2% SDS for 30 min at 55 °C and probed again with anti-β-actin monoclonal antibody to estimate the protein equal loading.…”

<p>Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer</p>

“…28 Lidocaine repressed lung cancer cell proliferation and metastasis by modulating miR-539/EGFR pathway. 29 In CRC, Qu et al discovered that lidocaine suppressed proliferation and stimulated apoptosis via the regulation of miR-520a-3p/EGFR. 10 Therefore, the underlying ncRNAs pathway in the action of lidocaine on CRC cells was investigated.…”

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

“…As reviewed in this paper, we noticed that the applied doses/concentrations of lidocaine varied when it came to different effects. For in vitro studies, lidocaine may work as chemosensitizer at relatively lower concentrations—for example, lower than 200 μM—while it requires a higher concentration to kill cancer cells, from 8 mM ( Sun and Sun, 2019 ) up to 4 M (administered topically), which is unachievable in clinical practice, in killing tongue cancer cells ( Sakaguchi et al, 2006 ). There is also research showing that under clinically relevant concentrations (0.1–200 μM), lidocaine exhibited anticancer efficacies.…”

“…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.…”