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Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF)
Author(s) -
Mammoto Tadanori,
Higashiyama Shigeki,
Mukai Mutsuko,
Mammoto Akiko,
Ayaki Masako,
Mashimo Takashi,
Hayashi Yukio,
Kishi Yoshihiko,
Nakamura Hiroyuki,
Akedo Hitoshi
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10145
Subject(s) - epidermal growth factor , lidocaine , pharmacology , ectodomain , growth factor , infiltration (hvac) , local anesthetic , anesthetic , cancer research , biology , chemistry , microbiology and biotechnology , medicine , receptor , anesthesia , biochemistry , neuroscience , physics , thermodynamics
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 Ca 2+ 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. © 2002 Wiley‐Liss, Inc.