Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
Toxicol In Vitro. 2011 Feb;25(1):160-6. doi: 10.1016/j.tiv.2010.10.013. Epub 2010 Oct 29.
As iron ions may participate in the pathogenesis of cancer and viral infections, the aim of this study was to monitor their influence on proliferation, E6 and E7 oncogene expression and reactive oxygen species (ROS) production in two human papilloma virus (HPV) positive cervical carcinoma cell lines (HeLa and SiHa) and one HPV negative vulvar cell line (A431). The anti-anaemic drug, ferric-sorbitol-citric acid complex (FSC) as a source of Fe(III) ions was used. Cells were treated with FSC at the concentrations between 0.001 and 1 mM Fe(III) for different time periods. Fe(III) ions inhibited the viability of HeLa and A431 cells while it had no influence on SiHa cells. Furthermore, Fe(III) treatment showed a time-dependent and a higher stimulatory effect on E6/E7 expression in SiHa cells than in HeLa cells. Fe(III) ion treatment with concentrations lower than 0.1mM showed a time and a concentration dependent intracellular ROS production in all tested cell lines, while the treatment with 1mM concentration decreased ROS production in all tested cell lines. In conclusion, Fe(III) ion treatment apart from having an anti-tumour effect, as we previously described, enhances survival of HPV 16-positive cells and might be associated with HPV oncogenesis.
由于铁离子可能参与癌症和病毒感染的发病机制，本研究旨在监测其对两种人乳头瘤病毒（HPV）阳性宫颈癌细胞系（HeLa 和 SiHa）和一种 HPV 阴性外阴细胞系（A431）增殖、E6 和 E7 癌基因表达和活性氧（ROS）产生的影响。使用抗贫血药物、柠檬酸高铁（FSC）作为 Fe(III)离子的来源。将细胞用浓度在 0.001 至 1mM Fe(III)之间的 FSC 处理不同时间。Fe(III)离子抑制了 HeLa 和 A431 细胞的活力，但对 SiHa 细胞没有影响。此外，Fe(III)处理显示出对 SiHa 细胞中 E6/E7 表达的时间依赖性和更高的刺激作用，比 HeLa 细胞更强。用低于 0.1mM 的浓度处理 Fe(III)离子在所有测试的细胞系中表现出时间和浓度依赖性的细胞内 ROS 产生，而用 1mM 浓度处理则降低了所有测试的细胞系中的 ROS 产生。总之，除了我们之前描述的抗肿瘤作用外，Fe(III)离子处理还增强了 HPV 16 阳性细胞的存活，并且可能与 HPV 致癌作用有关。
