The Antiproliferative Effect of Lidocaine on Human Tongue Cancer Cells with Inhibition of the Activity of Epidermal Growth Factor Receptor

In Brief Local anesthetics suppress proliferation in several cancer cells. The mechanism of the suppression, however, is unknown. Our previous study shows that lidocaine, at the level of tissue concentration under topical or local administration, has a direct inhibitory effect on the activity of epidermal growth factor receptor (EGFR), which is a potential target for antiproliferation in cancer cells. Therefore, we hypothesized that lidocaine would suppress the proliferation of cancer cells through the inhibition of EGFR activity. We investigated the effects of lidocaine (40–4000 μM) on proliferation of a human tongue cancer cell line, CAL27, which has a high level of EGFR expression, and also examined the effect of lidocaine on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR in CAL27 cells. A clinical concentration of lidocaine (400 μM) suppressed both serum-induced and EGF-induced proliferation of CAL27 cells and inhibited EGF-stimulated tyrosine kinase activity of EGFR without cytotoxicity. A larger concentration of lidocaine (4000 μM) showed cytotoxicity with an antiproliferative effect. We suggest that the inhibition of EGF-stimulated EGFR activity is one of the mechanisms of the antiproliferative effect of lidocaine on CAL27 cells. Lidocaine administered topically within the oral cavity for cancer pain relief may suppress the proliferation of human tongue cancer cells. IMPLICATIONS: Topical local anesthetics are used for cancer pain relief and may suppress the proliferation of cancer cells. We investigated the effects of lidocaine on proliferation of the human tongue cancer cell line CAL27. A clinical concentration of lidocaine suppressed the proliferation of CAL27 with inhibition of the activity of the epidermal growth factor receptor.