Nicotine, lung and cancer.
Nicotine, lung and cancer.
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DOI：
10.2174/187152007781058587
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发表时间：
2007-06
影响因子：
2.8
通讯作者：
Alessia Grozio;A. Catassi;Z. Cavalieri;L. Paleari;A. Cesario;P. Russo
中科院分区：
文献类型：
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作者：
Alessia Grozio;A. Catassi;Z. Cavalieri;L. Paleari;A. Cesario;P. Russo
呼吸道上皮表达胆碱能系统，包括烟碱受体(NAChRs)。据报道，作为鳞状细胞癌前体的正常人支气管上皮细胞(BEC)和作为腺癌前体的小气道上皮细胞(SAEC)的nAChRs谱略有不同。研究表明，肺癌或间皮瘤上表达的nAChRs形成了促进肿瘤细胞生长的自分泌增殖网络的一部分；其他研究表明，尼古丁可以促进结肠癌、胃癌和肺癌的生长。尼古丁和结构相关的致癌物NNK[4-(甲基亚硝氨基)-1-(3-吡啶)-1-丁酮]和NNN(N‘-亚硝基烟碱)可诱导多种小细胞肺癌细胞系和内皮细胞的增殖，尼古丁在包括肺在内的非神经组织中诱导生长因子(bFGF、转化生长因子-α、血管内皮生长因子和PDGF)的分泌，上调钙痛家族蛋白COX-2和VEGFR-2的表达。导致最终激活Raf/MAPK激酶/ERK(Raf/MEK/ERK)通路，从而促进通过烟草烟雾或香烟替代品暴露于尼古丁的肿瘤的生长和发展。已经证明尼古丁在体内促进实体肿瘤的生长，这表明它可能会诱导已经开始的肿瘤的进展。虽然烟草致癌物可以启动和促进肿瘤的发生，但接触尼古丁可能会使早期肿瘤具有增殖优势，但没有证据表明尼古丁本身会引发癌症。尼古丁可以防止各种药物诱导的细胞凋亡，如非小细胞肺癌的化疗药物，这一发现也支持了这一点，这也赋予了生存优势。
The respiratory epithelium expresses the cholinergic system including nicotinic receptors (nAChRs). It was reported that normal human bronchial epithelial cells (BEC), which are the precursor for squamous cell carcinomas, and small airway epithelial cells (SAEC), which are the precursor for adenocarcinomas, have slightly different repertoires of nAChRs. Studies shown that nAChRs expressed on lung carcinoma or mesothelioma form a part of an autocrine-proliferative network facilitating the growth of neoplastic cells; others demonstrated that nicotine can promote the growth of colon, gastric, and lung cancers. Nicotine and structurally related carcinogens like NNK [4-(methylnitrosoamino)- 1-(3-pyridyl)-1-butanone] and NNN (N'-nitrosonornicotine) could induce the proliferation of a variety of small cell lung carcinoma cell lines and endothelial cells and nicotine in non-neuronal tissues -including lung- induces the secretion of growth factors (bFGF, TGF-alpha, VEGF and PDGF), up regulation of the calpain family proteins, COX-2 and VEGFR-2, causing the eventual activation of Raf/MAPK kinase/ERK (Raf/MEK/ERK) pathway contributing to the growth and progression of tumors exposed to nicotine through tobacco smoke or cigarette substitutes. It has been demonstrated that nicotine promotes the growth of solid tumors in vivo, suggesting that might induce the progression of tumors already initiated. While tobacco carcinogens can initiate and promote tumorigenesis, the exposure to nicotine could confer a proliferative advantage to early tumors but there is no evidence that nicotine itself provokes cancer. This is supported by the findings that nicotine can prevent apoptosis induced by various agents - such as chemotherapeutic in NSCLC, conferring a survival advantage as well.