Lidocaine inhibits the metastatic potential of ovarian cancer by blocking Na<sub>V</sub>1.5‐mediated EMT and FAK/Paxillin signaling pathway

Liu, Chang; Yu, Miao; Li, Yi; Wang, Hao; Xu, Chi; Zhang, Xiaoqing; Li, Min; Guo, Hongyan; Ma, Ding; Guo, Xiangyang

doi:10.1002/cam4.3621

Cited by 32 publications

(26 citation statements)

References 37 publications

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“…Lidocaine is a local anesthetic drug derived from cocaine, and widely used in clinical application such as anti-bacteria, anti-inflammation, local skin anesthesia and so on ( Caracas et al, 2009 ; Adler et al, 2017 ; Cizmarikova et al, 2020 ). An increasing number of evidences have demonstrated that lidocaine could affect the development of multiple tumors including ovarian and breast cancer ( Gao et al, 2018 ; Khan et al, 2019 ; Liu et al, 2021 ). For example, it was reported that intravenous infusion of lidocaine during operation was associated with improved overall survival of patients with pancreatic cancer ( Zhang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Gao and colleagues suggested that the administration of lidocaine could enhance the apoptosis of breast cancer cells caused by cisplatin, as well as alleviating their metastasis in vivo ( Gao et al, 2018 ). Moreover, lidocaine could also suppress the growth and metastasis of ovarian cancer ( Liu et al, 2021 ). However, whether ferroptosis is involved in the function of lidocaine in breast and ovarian cancer is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Sun

Zhang

2021

Front. Pharmacol.

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Ovarian and breast cancer are prevalent female malignancies with increasing occurrence incidence and metastasis, significantly affecting the health and life quality of women globally. Anesthetic lidocaine has presented anti-tumor activities in the experimental conditions. However, the effect of lidocaine on ovarian and breast cancer remains elusive. We identified the important function of lidocaine in enhancing ferroptosis and repressing progression of ovarian and breast cancer. Our data showed that lidocaine further repressed erastin-inhibited ovarian and breast cancer cell viabilities. The treatment of lidocaine induced accumulation of Fe2+, iron and lipid reactive oxygen species (ROS) in ovarian and breast cancer cells. The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, we found that lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. The inhibition of miR-382-5p blocked lidocaine-induced ferroptosis of ovarian and breast cancer cells. MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro. The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo, in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. The clinical value of lidocaine in the treatment of ovarian and breast cancer deserves to be proved in detail.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Sun

Zhang

2021

Front. Pharmacol.

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“…As regards the local anesthetics, retrospective studies have revealed that the use of these drugs for regional anesthesia during perioperative period reduced the recurrence rate of patients with breast cancer [46]. In keeping with this, in vitro experiments demonstrated that bupivacaine and lidocaine inhibited OC cells proliferation and metastasis by blocking Nav1.5, confirming their role as potential anticancer agents [47,48]. The multi-effects of lidocaine were also confirmed in vivo, by using murine syngeneic OC (ID8) model.…”

Section: Figure 1 Ion Channels Expression In Ovarian Cancer (Oc)mentioning

confidence: 77%

“…The multi-effects of lidocaine were also confirmed in vivo, by using murine syngeneic OC (ID8) model. The molecular mechanism by which lidocaine hampers OC malignancy was recently studied by Liu and collaborators, who demonstrated that lidocaine binding to Nav1.5 blocked the activation of FAK/Paxillin signaling pathway, inhibiting proliferation and metastasis, and decreased cisplatin resistance of OC cells [48]. However, it should be noted that these compounds might elicit their anticancer effects also through mechanisms other than VGSC inhibition.…”

Section: Figure 1 Ion Channels Expression In Ovarian Cancer (Oc)mentioning

confidence: 99%

“…In vitro experiments showed that lidocaine enhanced OC cells sensitivity to cisplatin by blocking Nav1.5 and FAK/Paxillin signaling pathway. The OC cells treated with cisplatin and lidocaine combination expressed higher levels of apoptotic proteins such as caspase-3 and 8, and lower level of the antiapoptotic protein Bcl-2 [48]. Thus, targeting these channels maybe a promising strategy for overcoming cisplatin resistance.…”

Section: Ion Channels and Drug Resistancementioning

confidence: 99%

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Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Altamura

Greco

Carratù

et al. 2021

Cancers

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Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

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The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial‐to‐mesenchymal transition

et al. 2022

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Background: Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve-derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. Methods: Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH-SY5Y cells were co-cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI-specific therapeutic effects by blocking the GAL/GALR2 axis. Results: GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p < 0.05). Nerve-derived GAL activated GALR2 expression in SACC cells and induced epithelial-tomesenchymal transition (EMT) in SACC cells. Adding human recombinant GAL to the co-culture system promoted the proliferation, migration, and invasion of SACC cells significantly, but inhibited the apoptosis of SACC cells. Adding M871, a specific antagonist of GALR2, significantly blocked the above effects (p < 0.05) and inhibited the PNI of SACC cells in vitro and in vivo (p < 0.05). Conclusions: This study demonstrated that nerve-derived GAL activated GALR2 expression, and promoted EMT in SACC cells, thereby enhancing the | 4497 WANG et al. How to cite this article: Wang J, Yang Z, Liu Y, et al. The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition.

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Lidocaine inhibits the metastatic potential of ovarian cancer by blocking Na_V1.5‐mediated EMT and FAK/Paxillin signaling pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 32 publications

References 37 publications

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial‐to‐mesenchymal transition

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Lidocaine inhibits the metastatic potential of ovarian cancer by blocking NaV1.5‐mediated EMT and FAK/Paxillin signaling pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 32 publications

References 37 publications

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer

Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial‐to‐mesenchymal transition

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Lidocaine inhibits the metastatic potential of ovarian cancer by blocking Na_V1.5‐mediated EMT and FAK/Paxillin signaling pathway