Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF).
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.
Mammoto
Tadanori
T
Department of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. tada@qb4.so-net.ne.jp
Higashiyama
Shigeki
S
Mukai
Mutsuko
M
Mammoto
Akiko
A
Ayaki
Masako
M
Mashimo
Takashi
T
Hayashi
Yukio
Y
Kishi
Yoshihiko
Y
Nakamura
Hiroyuki
H
Akedo
Hitoshi
H
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008012:Lidocaine / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000779:Anesthetics, Local; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D006493:Heparin; D008012:Lidocaine; D066246:ErbB Receptors; D002118:Calcium