Wang Chengze, Gu Weiting, Zhang Yunpeng, Ji Yawen, Wen Yong, Xu Xin
School of Stomatology, Shandong University, PR China; Shandong Provincial Key Laboratory of Oral Tissue Regeneration, PR China.
Qilu hospital of Shandong University, PR China.
Exp Toxicol Pathol. 2017 Jul 5;69(6):402-407. doi: 10.1016/j.etp.2017.03.006. Epub 2017 Apr 3.
Cigarette smoking is one of highly risk factors of cervical cancer. Recently nicotine has been reported to increase proliferation and invasion in some smoking related cancers, like non-small cell lung cancer and esophageal squamous cell cancer. However, the effects and mechanisms of nicotine stimulation on cervical cancer cells are not clear. Here, we investigated the effects and mechanisms of nicotine stimulation on HeLa cells in vitro. In our study, we found that nicotine could accelerate HeLa cells migration and invasion, activate PI3K/Akt and NF-κB pathways and increase the expression of Vimentin in vitro. Moreover, we demonstrated that the specific PI3K inhibitor LY294002 could reverse nicotine-induced cell migration and invasion, NF-κB activation and up-regulation of Vimentin. Inhibition of NF-κB by Pyrrolidine dithiocarbamate (PDTC) also antagonized nicotine-induced cell migration, invasion and up-regulation of Vimentin. Simply put, these findings suggest that nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro.
吸烟是宫颈癌的高风险因素之一。最近有报道称,尼古丁会增加某些与吸烟相关癌症(如非小细胞肺癌和食管鳞状细胞癌)中的细胞增殖和侵袭。然而,尼古丁刺激对宫颈癌细胞的影响及机制尚不清楚。在此,我们在体外研究了尼古丁刺激对HeLa细胞的影响及机制。在我们的研究中,我们发现尼古丁可加速HeLa细胞迁移和侵袭,激活PI3K/Akt和NF-κB通路,并在体外增加波形蛋白的表达。此外,我们证明特异性PI3K抑制剂LY294002可逆转尼古丁诱导的细胞迁移和侵袭、NF-κB激活以及波形蛋白的上调。用吡咯烷二硫代氨基甲酸盐(PDTC)抑制NF-κB也可拮抗尼古丁诱导的细胞迁移、侵袭以及波形蛋白的上调。简而言之,这些发现表明尼古丁在体外通过激活PI3k/Akt/NF-κB通路促进宫颈癌细胞系HeLa的迁移和侵袭。