RRC ID 41621
Author Mammoto T, Higashiyama S, Mukai M, Mammoto A, Ayaki M, Mashimo T, Hayashi Y, Kishi Y, Nakamura H, Akedo H.
Title Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF).
Journal J. Cell. Physiol.
Abstract Although the mechanism is unknown, infiltration anesthetics are believed to have membrane-stabilizing action. We report here that such a most commonly used anesthetic, lidocaine, effectively inhibited the invasive ability of human cancer (HT1080, HOS, and RPMI-7951) cells at concentrations used in surgical operations (5-20 mM). Ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF) from the cell surface plays an important role in invasion by HT1080 cells. Lidocaine reduced the invasion ability of these cells by partly inhibiting the shedding of HB-EGF from the cell surface and modulation of intracellular Ca2+ concentration contributed to this action. The anesthetic action of lidocaine (sodium channel blocking ability) did not contribute to this anti-invasive action. In addition, lidocaine (5-30 mM), infiltrated around the inoculation site, inhibited pulmonary metastases of murine osteosarcoma (LM 8) cells in vivo. These data point to previously unrecognized beneficial actions of lidocaine and suggest that lidocaine might be an ideal infiltration anesthetic for surgical cancer operations.
Volume 192(3)
Pages 351-8
Published 2002-9
DOI 10.1002/jcp.10145
PMID 12124780
MeSH Anesthetics, Local / pharmacology* Animals Calcium / metabolism Cell Membrane / metabolism Cell Movement / drug effects Epidermal Growth Factor / metabolism* ErbB Receptors / genetics Heparin / metabolism Heparin-binding EGF-like Growth Factor Humans Intercellular Signaling Peptides and Proteins Lidocaine / pharmacology* Lung Neoplasms / prevention & control Lung Neoplasms / secondary Mice Mice, Inbred C3H Neoplasm Invasiveness / physiopathology Transcriptional Activation / drug effects Tumor Cells, Cultured
IF 3.923
Times Cited 21
Human and Animal Cells