Paleari L, Catassi A, Ciarlo M, Cavalieri Z, Bruzzo C, Servent D, Cesario A, Chessa L, Cilli M, Piccardi F, Granone P, Russo P
Lung Cancer Unit, National Cancer Research Institute, Genoa, Italy.
Cell Prolif. 2008 Dec;41(6):936-59. doi: 10.1111/j.1365-2184.2008.00566.x.
Lung cancer is the most common cause of cancer death in the world. Cigarette smoking represents the major risk factor. Nicotine, an active component of cigarettes, can induce cell proliferation, angiogenesis and apoptosis resistance. All these events are mediated through the nicotinic acetylcholine receptor (nAChR) expressed on lung cancer cells. We speculate that new insights into the pathophysiological roles of nAChR may lead to new therapeutic avenues to reduce non-small cell lung cancer (NSCLC) tumour growth.
Human samples of NSCLC, cell lines and mouse models were utilized in Western blotting, reverse transcriptase polymerase chain reaction and apoptosis studies.
Human NSCLC tissues expressed alpha7-nAChR. This expression was higher in smoking patients with squamous carcinomas than those with adenocarcinomas and in male smoking patients than in females. All the data support the hypothesis that major expression of alpha7-nAChR is related to major activation of the Rb-Raf-1/phospho-ERK/phospho-p90RSK pathway. alpha7-nAChR antagonists, via mitochondria associated apoptosis, inhibited proliferation of human NSCLC primary and established cells. Nicotine stimulates tumour growth in a murine model, A549 cells orthotopically grafted. The effects of nicotine were associated with increases in phospho-ERK in tumours. Proliferation effects of nicotine could be blocked by inhibition of alpha7-nAChR by the high affinity ligand alpha-cobratoxin.
These results showed that alpha7-nAChR plays an important role in NSCLC cell growth and tumour progression as well as in cell death.
肺癌是全球癌症死亡的最常见原因。吸烟是主要风险因素。尼古丁作为香烟的活性成分，可诱导细胞增殖、血管生成和抗凋亡。所有这些事件均通过肺癌细胞上表达的烟碱型乙酰胆碱受体（nAChR）介导。我们推测，对nAChR病理生理作用的新见解可能会带来减少非小细胞肺癌（NSCLC）肿瘤生长的新治疗途径。
在蛋白质免疫印迹、逆转录聚合酶链反应和凋亡研究中使用了NSCLC的人类样本、细胞系和小鼠模型。
人类NSCLC组织表达α7-nAChR。这种表达在吸烟的鳞状细胞癌患者中高于腺癌患者，在男性吸烟患者中高于女性。所有数据均支持以下假设：α7-nAChR的主要表达与Rb-Raf-1/磷酸化-ERK/磷酸化-p90RSK途径的主要激活有关。α7-nAChR拮抗剂通过线粒体相关凋亡抑制人NSCLC原代细胞和已建立细胞系的增殖。尼古丁在原位移植A549细胞的小鼠模型中刺激肿瘤生长。尼古丁的作用与肿瘤中磷酸化-ERK的增加有关。尼古丁的增殖作用可被高亲和力配体α-银环蛇毒素抑制α7-nAChR所阻断。
这些结果表明，α7-nAChR在NSCLC细胞生长、肿瘤进展以及细胞死亡中起重要作用。
