Deng Xingming
Division of Cancer Biology, Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Scientifica (Cairo). 2014;2014:215426. doi: 10.1155/2014/215426. Epub 2014 May 20.
Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells. In contrast to nicotine, NNK is a more potent carcinogen that not only induces single-strand DNA breaks and oxidative DNA damage but also stimulates survival and proliferation of normal lung epithelial and lung cancer cells. However, the molecular mechanism(s) by which nicotine and NNK promote cell survival, proliferation, and lung tumor development remains elusive. The fate of cells (i.e., survival or death) is largely decided by the Bcl2 family members. In the past several years, multiple signaling links between nicotine/NNK and Bcl2 family members have been identified that regulate survival and proliferation. This review provides a concise, systematic overview of the current understanding of the role of the pro- or antiapoptotic proteins in cigarette smoking, lung cancer development, and treatment resistance.
肺癌是癌症死亡的主要原因，且与吸烟存在很强的病因学关联。尼古丁和亚硝胺4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮（NNK）是香烟烟雾中的两种主要成分，它们对人类肺癌的发展有显著影响。尼古丁能够刺激正常人类肺上皮细胞和肺癌细胞的存活。与尼古丁不同，NNK是一种更强效的致癌物，它不仅会导致单链DNA断裂和氧化性DNA损伤，还会刺激正常肺上皮细胞和肺癌细胞的存活与增殖。然而，尼古丁和NNK促进细胞存活、增殖以及肺癌发展的分子机制仍不清楚。细胞的命运（即存活或死亡）很大程度上由Bcl2家族成员决定。在过去几年中，已确定尼古丁/NNK与Bcl2家族成员之间存在多种调节存活和增殖的信号联系。本综述简要、系统地概述了目前对促凋亡或抗凋亡蛋白在吸烟、肺癌发展和治疗耐药性中的作用的理解。
