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 |
2002-9-1
|
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 |
5.546
|
Times Cited |
39
|
WOS Category
|
PHYSIOLOGY
CELL BIOLOGY
|
Resource |
Human and Animal Cells |
|