除了吸烟,肺癌可能是由其他因素引起的,包括镉等重金属,镍,砷,铍和六价铬[Cr(VI)],在多个设置中使用,导致广泛的环境和职业暴露以及大量使用。Cr(VI)引起肺癌的机制尚不完全清楚。目前,染色体不稳定是Cr(VI)诱导癌症发生机制的关键过程,先前的研究表明,Cr(VI)通过引发组织损伤和炎症而影响小鼠的肺组织。然而,Cr(VI)诱导炎症的机制及其在肺癌中的确切作用尚不清楚。因此,本综述旨在系统回顾以往评估Cr(VI)诱导炎症的研究,并总结Cr(VI)诱导炎症的主要炎症途径。在细胞培养研究中,COX2,VEGF,JAK-STAT,白三烯B4(LTB4),MAPK,NF-κB和Nrf2信号通路被Cr(VI)一致上调,清楚地表明这些途径与Cr(VI)诱导的炎症有关。此外,Akt信号也被证明有助于Cr(VI)诱导的炎症,尽管报告了不同的发现。在动物模型中很少进行机械研究,其中Cr(VI)上调氧化途径,肺组织中NF-kB信号和MAPK通路。类似于细胞培养研究,报告了Cr(VI)对Akt信号的相反作用。这项工作提供了对Cr(VI)诱导肺部炎症的机制的见解。然而,研究设计中的不同发现和其他主要问题,在细胞和动物模型中,提示需要进一步的研究来揭示Cr(VI)诱导的炎症机制及其在肺癌中的作用。
Besides smoking, lung cancer can be caused by other factors, including heavy metals such as cadmium, nickel, arsenic, beryllium and hexavalent chromium [Cr(VI)], which is used in multiple settings, resulting in widespread environmental and occupational exposures as well as heavy use. The mechanism by which Cr(VI) causes lung cancer is not completely understood. Currently, it is admitted chromosome instability is a key process in the mechanism of Cr(VI)-induced cancer, and previous studies have suggested Cr(VI) impacts the lung tissue in mice by triggering tissue damage and inflammation. However, the mechanism underlying Cr(VI)-induced inflammation and its exact role in lung cancer are unclear. Therefore, this
review aimed to systematically examine previous studies assessing Cr(VI)-induced inflammation and to summarize the major inflammatory pathways involved in Cr(VI)-induced inflammation. In cell culture studies, COX2, VEGF, JAK-STAT, leukotriene B4 (LTB4), MAPK, NF-ҡB and Nrf2 signaling pathways were consistently upregulated by Cr(VI), clearly demonstrating that these pathways are involved in Cr(VI)-induced inflammation. In addition, Akt signaling was also shown to contribute to Cr(VI)-induced inflammation, although discrepant findings were reported. Few mechanistic studies were performed in animal models, in which Cr(VI) upregulated oxidative pathways, NF-kB signaling and the MAPK pathway in the lung tissue. Similar to cell culture studies, opposite effects of Cr(VI) on Akt signaling were reported. This work provides insights into the mechanisms by which Cr(VI) induces lung inflammation. However, discrepant findings and other major issues in study design, both in cell and animal models, suggest that further studies are required to unveil the mechanism of Cr(VI)-induced inflammation and its role in lung cancer.