Faculty Collaboration Database

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

07/19/2002

Pubmed ID

12124780

DOI

10.1002/jcp.10145

Scopus ID

2-s2.0-0036321571 (requires institutional sign-in at Scopus site)   56 Citations

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.

Author List

Mammoto T, Higashiyama S, Mukai M, Mammoto A, Ayaki M, Mashimo T, Hayashi Y, Kishi Y, Nakamura H, Akedo H

Authors

Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tadanori 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, Local
Animals
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