Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF). J Cell Physiol 2002 Sep;192(3):351-8
Date
07/19/2002Pubmed ID
12124780DOI
10.1002/jcp.10145Scopus ID
2-s2.0-0036321571 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Mammoto T, Higashiyama S, Mukai M, Mammoto A, Ayaki M, Mashimo T, Hayashi Y, Kishi Y, Nakamura H, Akedo HAuthors
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinTadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Anesthetics, LocalAnimals
Calcium
Cell Membrane
Cell Movement
Epidermal Growth Factor
ErbB Receptors
Heparin
Heparin-binding EGF-like Growth Factor
Humans
Intercellular Signaling Peptides and Proteins
Lidocaine
Lung Neoplasms
Mice
Mice, Inbred C3H
Neoplasm Invasiveness
Transcriptional Activation
Tumor Cells, Cultured