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Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase

التفاصيل البيبلوغرافية
العنوان: Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase
المؤلفون: Piegeler, T, Schläpfer, M, Dull, R O, Schwartz, D E, Borgeat, A, Minshall, R D, Beck-Schimmer, B
المصدر: Piegeler, T; Schläpfer, M; Dull, R O; Schwartz, D E; Borgeat, A; Minshall, R D; Beck-Schimmer, B (2015). Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase. British Journal of Anaesthesia, 115(5):784-791.
بيانات النشر: Oxford University Press
سنة النشر: 2015
المجموعة: University of Zurich (UZH): ZORA (Zurich Open Repository and Archive
مصطلحات موضوعية: Institute of Physiology, Zurich Center for Integrative Human Physiology (ZIHP), Institute of Anesthesiology, 610 Medicine & health, Anesthesiology and Pain Medicine
الوصف: BACKGROUND Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. METHODS NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml(-1)) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. RESULTS Ropivacaine (1 nM-100 μM) and lidocaine (1-100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10(-6) M for lidocaine; IC50=1.52×10(-10) M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). CONCLUSIONS At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasis.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: German
English
تدمد: 0007-0912
العلاقة: https://www.zora.uzh.ch/id/eprint/117548/1/PiegelerT%202015.pdfTest; https://www.zora.uzh.ch/id/eprint/117548/9/1-s2.0-S0007091217310814-main.pdfTest; https://www.zora.uzh.ch/id/eprint/117548/17/ZORA_NL_117548.pdfTest; info:pmid/26475807; urn:issn:0007-0912
DOI: 10.5167/uzh-117548
DOI: 10.1093/bja/aev341
الإتاحة: https://doi.org/10.5167/uzh-11754810.1093/bja/aev341Test
https://www.zora.uzh.ch/id/eprint/117548Test/
https://www.zora.uzh.ch/id/eprint/117548/1/PiegelerT%202015.pdfTest
https://www.zora.uzh.ch/id/eprint/117548/9/1-s2.0-S0007091217310814-main.pdfTest
https://www.zora.uzh.ch/id/eprint/117548/17/ZORA_NL_117548.pdfTest
حقوق: info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.36122AC0
قاعدة البيانات: BASE
الوصف
تدمد:00070912
DOI:10.5167/uzh-117548