Anti-tumor effects of lidocaine on human gastric cancer cells in vitro

Ye, L; Zhang, Y; Chen, Y J; Liu, Q

doi:10.4149/bll_2019_036

Cited by 37 publications

(39 citation statements)

References 28 publications

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“…Intravenous lidocaine injections may effectively relieve pain and reduce fentanyl consumption during the early postoperative period (28). Recent studies have demonstrated a possible regulatory mechanism of action for lidocaine through suppressing the proliferation of gastric cancer cells, which is associated with ERK1/2 phosphorylation, the MAPK pathway and altering the expression profiles of microRNAs (3)(4)(5). EMT activation is involved in the cell invasion and metastasis of a variety of cancer types (29,30).…”

Section: Discussionmentioning

confidence: 99%

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Lidocaine suppresses the malignant behavior of gastric cancer cells via the c‑Met/c‑Src pathway

et al. 2021

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The present study was designed to investigate the role and mechanism of action behind the action of lidocaine in gastric cancer cells. Lidocaine was tested for its potential role in affecting the viability of cells using Cell Counting Kit-8 (CCK-8) assays. It was found that there was a decreased MKN45 cell viability upon lidocaine treatment in a dose-dependent manner. Phosphorylated c-Met, phosphorylated c-Src, c-Met and c-Src levels were detected using western blotting following lidocaine or hepatocyte growth factor (HGF) intervention. It was found that the phosphorylation levels of c-Met and c-Src were markedly reduced by lidocaine treatment, with this effect being further relieved by the addition of HGF. Subsequently, whether lidocaine repressed the malignant biological properties of gastric cancer cells through the c-Met/c-Src axis was further investigated through the detection of epithelial-mesenchymal transition markers (N-caderin and vimentin), wound healing and transwell assay analysis. In addition, cell apoptosis and the levels of apoptosis-related proteins were determined using TUNEL and western blot assays, respectively. The results demonstrated that the malignant behavior of cells were notably repressed upon lidocaine treatment, but the addition of HGF markedly reversed these effects, indicating that the effects of lidocaine on supressing the malignant behaviour of cells could be mediated through the c-Met/c-Src axis. Subsequently, whether lidocaine affected the sensitivity of cells to cisplatin or 5-FU was analyzed using a CCK-8 assay. Enhanced sensitivity of cells to cisplatin or 5-FU was observed when treated in combination with lidocaine. The present study concluded that the involvement of the c-Met/c-Src pathway in the biological behaviour of MKN45 cells was mediated by lidocaine. Therefore, lidocaine may have the potential to suppress the malignant behaviour and proliferation of gastric cancer cells.

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Section: Discussionmentioning

confidence: 99%

“…Lidocaine is a local anesthetic which can effectively inhibit the biological activity of a variety of cancer types. In vivo and in vitro studies have indicated the antitumor effects of lidocaine in gastric cancer (3)(4)(5). Mechanistically, lidocaine has been found to decrease Src activation (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Lidocaine suppresses the malignant behavior of gastric cancer cells via the c‑Met/c‑Src pathway

et al. 2021

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“…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. However, further studies are warranted to confirm its exact targets in different cancer types.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

“…Another study conducted on human gastric cancer SGC7901 and BGC823 cells, lidocaine inhibited their proliferation, migration, and invasion and induced apoptosis in a concentration- (0.1–10 Mm, determined by MTT) and time- (0–72 h) dependent manner. Mechanistic studies showed that lidocaine increased the Bax/Bcl-2 ratio, increased the anti-apoptotic p-p38, and altered the MAPK expression, suggesting a mitochondria-mediated apoptosis pathway ( Ye L. et al, 2019 ).…”

Section: Lidocaine In Cancer Treatmentmentioning

confidence: 99%

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

Zhou

Wang

Cui

et al. 2020

Front. Cell Dev. Biol.

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While cancer treatment has improved dramatically, it has also encountered many critical challenges, such as disease recurrence, metastasis, and drug resistance, making new drugs with novel mechanisms an urgent clinical need. The term “drug repositioning,” also known as old drugs for new uses, has emerged as one practical strategy to develop new anticancer drugs. Anesthetics have been widely used in surgical procedures to reduce the excruciating pain. Lidocaine, one of the most-used local anesthetics in clinical settings, has been found to show multi-activities, including potential in cancer treatment. Growing evidence shows that lidocaine may not only work as a chemosensitizer that sensitizes other conventional chemotherapeutics to certain resistant cancer cells, but also could suppress cancer cells growth by single use at different doses or concentrations. Lidocaine could suppress cancer cell growth in vitro and in vivo via multiple mechanisms, such as regulating epigenetic changes and promoting pro-apoptosis pathways, as well as regulating ABC transporters, metastasis, and angiogenesis, etc., providing valuable information for its further application in cancer treatment and for new drug discovery. In addition, lidocaine is now under clinical trials to treat certain types of cancer. In the current review, we summarize the research and analyze the underlying mechanisms, and address key issues in this area.

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“…Local anesthetic used during the operation benefits cancer patients with breast cancer, common cancer and gastric cancer through suppressing the metastasis and recurrence of tumors [ 22 , 23 ]. Bupivacaine is one of the amide-linked local anesthetics.…”

Section: Discussionmentioning

confidence: 99%

Bupivacaine suppresses the progression of gastric cancer through regulating circ_0000376/miR-145-5p axis

Zhou

Miao

et al. 2020

BMC Anesthesiol

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Background Local anesthetic Bupivacaine commonly used in gastric cancer resection operation has been reported to suppress the progression of gastric cancer. However, the specific mechanism by which Bupivacaine functions is largely unexplored. Methods The viability and metastasis of gastric cancer cells were assessed by Cell counting kit-8 (CCK8) assay and transwell migration and invasion assays. The apoptosis was evaluated by caspase-3 activity detection assay and flow cytometry. The glycolysis was analyzed through detecting the extracellular acidification rate (ECAR) via Seahorse XF 96 Extracellular Flux Analyzer and the expression of glucose transporter type 1 (GLUT1) and lactic dehydrogenase A (LDHA) via Western blot assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circular RNA 0000376 (circ_0000376) and microRNA-145-5p (miR-145-5p). The interaction between circ_0000376 and miR-145-5p was predicted using Circular RNA Interactome database and validated by dual-luciferase reporter assay. Results Bupivacaine restrained the viability, metastasis and glycolytic process while promoted the apoptosis of gastric cancer cells. Bupivacaine decreased the level of circ_0000376 while enhanced the abundance of miR-145-5p in gastric cancer cells. Circ_0000376 accelerated the malignant behaviors of gastric cancer cells. MiR-145-5p directly interacted with circ_0000376 in gastric cancer cells, and miR-145-5p was negatively regulated by circ_0000376. The addition of circ_0000376 or the interference of miR-145-5p partly reversed Bupivacaine-mediated influences in gastric cancer cells. Conclusion Bupivacaine exerted an anti-tumor role to suppress the progression of gastric cancer through reducing the abundance of circ_0000376 and up-regulating miR-145-5p.

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Anti-tumor effects of lidocaine on human gastric cancer cells in vitro

Cited by 37 publications

References 28 publications

Lidocaine suppresses the malignant behavior of gastric cancer cells via the c‑Met/c‑Src pathway

Lidocaine suppresses the malignant behavior of gastric cancer cells via the c‑Met/c‑Src pathway

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

Bupivacaine suppresses the progression of gastric cancer through regulating circ_0000376/miR-145-5p axis

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