The antiproliferative effect of lidocaine on human tongue cancer cells with inhibition of the activity of epidermal growth factor receptor
The antiproliferative effect of lidocaine on human tongue cancer cells with inhibition of the activity of epidermal growth factor receptor
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DOI：
10.1213/01.ane.0000198330.84341.35
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发表时间：
2006-04-01
影响因子：
5.7
通讯作者：
Hirose, M
中科院分区：
文献类型：
--
作者：
Sakaguchi, M;Kuroda, Y;Hirose, M
局部麻醉剂抑制几种癌细胞的增殖。然而，抑制的机制尚不清楚。我们以前的研究表明，在局部或局部给药的组织浓度水平下，利多卡因对表皮生长因子受体（EGFR）的活性具有直接抑制作用，EGFR是抗癌细胞增殖的潜在靶点。因此，我们假设利多卡因通过抑制EGFR活性来抑制癌细胞的增殖。我们研究了利多卡因（40 - 4000 μ M）对人舌癌细胞系CAL 27增殖的影响，CAL 27具有高水平的EGFR表达，并且还检测了利多卡因对CAL 27细胞中表皮生长因子（EGF）刺激的EGFR自磷酸化的影响。临床浓度的利多卡因（400 μ M）抑制血清诱导和EGF诱导的CAL 27细胞增殖，并抑制EGF刺激的EGFR酪氨酸激酶活性，而无细胞毒性。较大浓度的利多卡因（4000 μ M）显示出细胞毒性和抗增殖作用。我们认为，抑制EGF刺激的EGFR活性是利多卡因抗CAL 27细胞增殖作用的机制之一。利多卡因口腔内局部给药用于缓解癌症疼痛可能抑制人舌癌细胞的增殖。
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 mu M) 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)-stimulateci au-tophosphorylation of EGFR in CAL27 cells. A clinical concentration of lidocaine (400 mu M) 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 mu M) 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.