Lidocaine inhibited migration of NSCLCA549 cells via the CXCR4 regulation
Autor: | Baichun Xing, Yanan Cui, Linlin Yang |
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Rok vydání: | 2022 |
Předmět: |
0301 basic medicine
Receptors CXCR4 Cancer Research Programmed cell death Lung Neoplasms Pharmacology Filamentous actin 03 medical and health sciences 0302 clinical medicine Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor Genetics Humans Viability assay Cell Proliferation A549 cell biology Chemistry CD44 Lidocaine Cell migration General Medicine Intercellular Adhesion Molecule-1 Actins Chemokine CXCL12 030104 developmental biology Oncology Apoptosis 030220 oncology & carcinogenesis biology.protein Calcium Intracellular |
Zdroj: | Cancer Biomarkers. 33:317-330 |
ISSN: | 1875-8592 1574-0153 |
Popis: | Background Lidocaine is a local anesthetic that wildly used in surgical treatment and postoperative medical care for lung cancers. We hypothesized that lidocaine at clinical plasma concentration can inhibit CXCL12/CXCR4 axis-regulated cytoskeletal remodeling thereby reduce the migration of Non-small-cell lung cancers (NSCLC) cells. Methods We determined the effect of lidocaine at clinical plasma concentration on CXCL12-induced cell viability, apoptosis, cell death, monolayer cell wound healing rate, individual cell migration indicators, expression of CXCR4, CD44, and ICAM-1, intracellular Ca2+ level, and filamentous actin level alteration of NSCLC cells A549 and CXCR4-knocked down A549 cells using CCK-8, Bcl-2 ELISA, Cell death ELISA, wound healing assay, chemotaxis assay, western blotting, QPCR, Fura-2-based intracellular Ca2+ assay, and Fluorescein Phalloidin staining respectively. Results Lidocaine did not affect cell viability, apoptosis, and cell death but inhibited CXCL12-induced migration, intracellular Ca2+ releasing, and filamentous actin increase. Lidocaine decreased expression of CXCR4, increased CD44, but had no effect on ICAM-1. CXCL12 induced the increase of CD44 and ICAM-1 but did not affect CD44 in the presence of lidocaine. The knockdown of CXCR4 eliminated all the effects of lidocaine. The overexpression of CXCR4 promoted migration but the migration was inhibited by lidocaine. Conclusion Lidocaine at clinical plasma concentrations inhibited CXCL12-induced CXCR4 activation, thereby reduced the intracellular Ca2+-dependent cytoskeleton remodeling, resulting in slower migration of A549 cells. |
Databáze: | OpenAIRE |
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