Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy
Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy
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DOI：
10.1158/1078-0432.ccr-10-2434
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发表时间：
2011-06-01
影响因子：
11.5
通讯作者：
Ho, Yuan-Soon
中科院分区：
文献类型：
--
作者：
Wu, Chih-Hsiung;Lee, Chia-Hwa;Ho, Yuan-Soon
烟碱型乙酰胆碱受体(NAChR)于1970年首次被鉴定为神经递质和离子通道的膜受体。NAChRs已被证明与多种类型的人类癌细胞中吸烟诱导的癌症形成有关。体外和体内动物研究表明，同五聚体nAChR抑制剂，如甲基乌头碱和α-BGTX，可以减弱尼古丁诱导的肺癌、结肠癌和膀胱癌细胞的增殖、血管生成和转移效应。最近的研究表明，α9-nAChR在乳腺癌的形成中起重要作用，在许多体内研究中，α9-nAChR特异性拮抗剂(如α-IMI、α-IMI、Vc1.1、RgIA和It14a)具有镇痛作用。Vc1.1在多种动物疼痛模型中发挥作用，目前已进入II期临床试验。在癌症治疗方面，已发现天然化合物如石油酚和EGCG通过抑制α9-nAChR信号通路来阻断尼古丁和雌激素诱导的乳腺癌细胞增殖。详细研究nAChRs及其特异性拮抗剂的致癌作用将有助于我们更好地理解它们作为临床翻译靶点的价值。临床癌症资源；17(11)；3533-41。(C)2011年AACR。
The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and alpha-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that alpha 9-nAChR is important for breast cancer formation, and in many in vivo studies, alpha 9-nAChR-specific antagonists (e.g., alpha-ImI, alpha-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine-and estrogen-induced breast cancer cell proliferation through inhibition of the alpha 9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation. Clin Cancer Res; 17(11); 3533-41. (C)2011 AACR.