Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
J Oncol. 2011;2011:456743. doi: 10.1155/2011/456743. Epub 2011 Mar 30.
Cigarette smoking is highly correlated with the onset of a variety of human cancers, and continued smoking is known to abrogate the beneficial effects of cancer therapy. While tobacco smoke contains hundreds of molecules that are known carcinogens, nicotine, the main addictive component of tobacco smoke, is not carcinogenic. At the same time, nicotine has been shown to promote cell proliferation, angiogenesis, and epithelial-mesenchymal transition, leading to enhanced tumor growth and metastasis. These effects of nicotine are mediated through the nicotinic acetylcholine receptors that are expressed on a variety of neuronal and nonneuronal cells. Specific signal transduction cascades that emanate from different nAChR subunits or subunit combinations facilitate the proliferative and prosurvival functions of nicotine. Nicotinic acetylcholine receptors appear to stimulate many downstream signaling cascades induced by growth factors and mitogens. It has been suggested that antagonists of nAChR signaling might have antitumor effects and might open new avenues for combating tobacco-related cancer. This paper examines the historical data connecting nicotine tumor progression and the recent efforts to target the nicotinic acetylcholine receptors to combat cancer.
吸烟与多种人类癌症的发生高度相关，而且持续吸烟已知会消除癌症治疗的有益效果。虽然烟草烟雾中含有数百种已知的致癌物质，但尼古丁是烟草烟雾中的主要成瘾成分，并不致癌。同时，尼古丁已被证明可促进细胞增殖、血管生成和上皮-间充质转化，从而导致肿瘤生长和转移增强。尼古丁的这些作用是通过存在于各种神经元和非神经元细胞上的烟碱型乙酰胆碱受体介导的。源自不同 nAChR 亚基或亚基组合的特定信号转导级联反应促进了尼古丁的增殖和生存功能。烟碱型乙酰胆碱受体似乎刺激了由生长因子和有丝分裂原诱导的许多下游信号转导级联反应。有人提出，nAChR 信号的拮抗剂可能具有抗肿瘤作用，并为对抗与烟草有关的癌症开辟新途径。本文考察了将尼古丁与肿瘤进展联系起来的历史数据，以及最近针对烟碱型乙酰胆碱受体来对抗癌症的努力。
