Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Toxicology. 2011 Jul 11;285(1-2):25-30. doi: 10.1016/j.tox.2011.03.016. Epub 2011 Apr 5.
Epidemiological studies have demonstrated a close correlation between nickel exposure and the incidence of lung cancer. Several studies have suggested that nickel contributes to tumor progression of human lung cancer. In this in vitro study, we found that nickel, as nickel chloride, could significantly enhance the invasive potential of human lung cancer cells, accompanied by elevated expression of IL-8, TGF-β, MMP2 and MMP9 in human lung cancer cells. Importantly, we demonstrated that nickel could activate TLR4 signaling in human lung cancer cells. Further studies showed that the TLR4/MyD88 signaling conferred the enhanced invasive potential of human lung cancer cells induced by nickel. Finally, we revealed that the p38MAPK pathway and NF-kB pathway were necessary for the enhanced invasive potential of human lung cancer cells induced by nickel. Our data provide a mechanistic explanation for nickel induced invasion of human lung cancer, and they suggest new strategies for nickel-related lung cancer clinical biotherapies.
流行病学研究表明，镍暴露与肺癌的发病率密切相关。多项研究表明，镍有助于促进人类肺癌的肿瘤进展。在这项体外研究中，我们发现镍（以氯化镍的形式存在）可以显著增强人类肺癌细胞的侵袭能力，同时伴随着人类肺癌细胞中 IL-8、TGF-β、MMP2 和 MMP9 的表达上调。重要的是，我们证明镍可以激活人类肺癌细胞中的 TLR4 信号通路。进一步的研究表明，TLR4/MyD88 信号通路赋予了镍诱导的人类肺癌细胞侵袭能力的增强。最后，我们揭示了 p38MAPK 通路和 NF-κB 通路是镍诱导的人类肺癌细胞侵袭能力增强所必需的。我们的数据为镍诱导的人类肺癌侵袭提供了机制解释，并为镍相关的肺癌临床生物治疗提供了新的策略。
