Lidocaine induces epithelial‑mesenchymal transition and aggravates cancer behaviors in non‑small cell lung cancer A549 cells

Hsieh,Wen-Hui; Liao,Shu-Wei; Chan,Shun-Ming; Hou,Jin-De; Wu,Szu-Yuan; Ho,Bing-Ying; Chen,Kung-Yen; Tai,Yu-Ting; Fang,Hsu-Wei; Fang,Chih-Yuan; Chen,Se-Yi; Lin,Jui-An

doi:10.3892/ol.2023.13932

Lidocaine induces epithelial‑mesenchymal transition and aggravates cancer behaviors in non‑small cell lung cancer A549 cells

Authors:
- Wen-Hui Hsieh
- Shu-Wei Liao
- Shun-Ming Chan
- Jin-De Hou
- Szu-Yuan Wu
- Bing-Ying Ho
- Kung-Yen Chen
- Yu-Ting Tai
- Hsu-Wei Fang
- Chih-Yuan Fang
- Se-Yi Chen
- Jui-An Lin
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Affiliations: Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei 10608, Taiwan, R.O.C., Department of Anesthesiology, Chi-Mei Medical Center, Tainan 71004, Taiwan, R.O.C., Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan, R.O.C., Division of Anesthesiology, Hualien Armed Forces General Hospital, Hualien 97144, Taiwan, R.O.C., Center for Regional Anesthesia and Pain Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan, R.O.C., Primo Biotechnology Co., Ltd., Taipei 10480, Taiwan, R.O.C., Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan, R.O.C., Division of Oral and Maxillofacial Surgery, Department of Dentistry, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan, R.O.C., Department of Neurosurgery, Chung-Shan Medical University, Taichung 40201, Taiwan, R.O.C., Department of Anesthesiology, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan, R.O.C.
Published online on: June 27, 2023 https://doi.org/10.3892/ol.2023.13932
Article Number: 346
Copyright: © Hsieh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The effects of clinically relevant concentrations of lidocaine on epithelial‑mesenchymal transition (EMT) and associated lung cancer behaviors have rarely been investigated. The aim of the present study was to assess the impact of lidocaine on EMT and its related phenomena, including chemoresistance. Lung cancer cell lines (A549 and LLC.LG) were incubated with various concentrations of lidocaine, 5‑fluorouracil (5‑FU) or both to test their effects on cell viability. Subsequently, the effects of lidocaine on various cell behaviors were assessed in vitro and in vivo using Transwell migration, colony‑formation and anoikis‑resistant cell aggregation assays, and human tumor cell metastasis in a chorioallantoic membrane (CAM) model quantitated by PCR analysis. Prototypical EMT markers and their molecular switch were analyzed using western blotting. In addition, a conditioned metastasis pathway was generated through Ingenuity Pathway Analysis. Based on these measured proteins (slug, vimentin and E‑cadherin), the molecules involved and the alteration of genes associated with metastasis were predicted. Of note, clinically relevant concentrations of lidocaine did not affect lung cancer cell viability or alter the effects of 5‑FU on cell survival; however, at this dose range, lidocaine attenuated the 5‑FU‑induced inhibitory effect on cell migration and promoted EMT. The expression levels of vimentin and Slug were upregulated, whereas the expression of E‑cadherin was downregulated. EMT‑associated anoikis resistance was also induced by lidocaine administration. In addition, portions of the lower CAM with a dense distribution of blood vessels exhibited markedly increased Alu expression 24 h following the inoculation of lidocaine‑treated A549 cells on the upper CAM. Thus, at clinically relevant concentrations, lidocaine has the potential to aggravate cancer behaviors in non‑small cell lung cancer cells. The phenomena accompanying lidocaine‑aggravated migration and metastasis included altered prototypical EMT markers, anoikis‑resistant cell aggregation and attenuation of the 5‑FU‑induced inhibitory effect on cell migration.

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