Selenium biomarkers in prostate cancer cell lines and influence of selenium on invasive potential of PC3 cells
Selenium biomarkers in prostate cancer cell lines and influence of selenium on invasive potential of PC3 cells
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DOI：
10.3389/fonc.2013.00239
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Fairweather-Tait, Susan
中科院分区：
文献类型：
--
作者：
Hendrickx, Wouter;Decock, Julie;Fairweather-Tait, Susan
膳食硒摄入量与降低癌症风险有关，但其潜在机制尚不清楚。我们质疑将人体血液中发现的硒浓度应用于体外研究的常用做法，并评估了生物标志物的效用，例如，谷胱甘肽过氧化物酶1（GPx 1）和硫氧还蛋白还原酶1（TrxR 1），以确定体外工作的适当硒水平。此外，我们研究了硒-甲基硒代半胱氨酸（SeMSC）对前列腺癌细胞迁移和侵袭的影响。在排除细胞毒性后，我们证明了前列腺癌细胞系对硒治疗的反应不同，如通过生物标志物评估所观察到的。我们发现，GPx 1活性和TrxR 1表达的最大水平达到较低的硒浓度在LNCaP相比，PC 3细胞，和PC 3相比DU 145细胞。因此，当使用硒补充的读数（包括使用硒响应生物标志物）进一步获知时，使用从人体研究中推断的硒浓度进行体外工作可能是适用的。在长期SeMSC处理后未观察到对PC 3迁移或侵袭的影响;然而，当在测定期间单独施用处理时，发现轻微增加。当细胞在低血清条件下培养时，可以观察到相反的情况，在长期而不是急性SeMSC处理后，迁移显著增加。总之，这些发现表明，在研究对生物过程的任何影响之前，或在比较模型之前，必须研究体外模型的硒敏感性，最好使用生物标志物。
Dietary selenium intake has been linked to reduced cancer risk, however the underlying mechanisms are yet unknown. We question the commonly used practice of applying selenium concentrations found in human blood to in vitro studies and evaluated the utility of biomarkers, e.g., glutathione peroxidase 1 (GPx1) and thioredoxin reductase 1 (TrxR1), to determine appropriate selenium levels for in vitro work. Furthermore, we investigated the effects of Se-methylselenocysteine (SeMSC) on prostate cancer cell migration and invasion. After excluding cytotoxicity, we demonstrated that prostate cancer cell lines respond differently to selenium treatment as observed through biomarker assessment. We found that the maximum levels of GPx1 activity and TrxR1 expression were reached at lower selenium concentrations in LNCaP compared to PC3 cells, and PC3 compared to DU145 cells. Therefore the use of selenium concentrations extrapolated from human studies for in vitro work may be applicable when further informed using a readout of selenium repletion including use of selenium responsive biomarkers. No effect on PC3 migration or invasion was observed after long term SeMSC treatment; however a slight increase was found when treatment was solely administered during the assay. The opposite could be observed when cells were cultured under low serum conditions, with a significant increase in migration upon long term but not upon acute SeMSC treatment. To conclude, these findings indicate that it is imperative to study the selenium sensitivity of an in vitro model preferably using biomarkers before investigating any effects on biological processes, or before comparing models.