Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants that are of increasing public concern worldwide. However, their relationship with colorectal cancer (CRC) is poorly understood. This study aims to comprehensively investigate the effect of PFOS and PFOA on the development and progression of CRC in vitro using a series of biological techniques and metabolic profiling. Herein, the migration of three-dimensional (3D) spheroids of two CRC cell lines, SW48 KRAS wide-type (WT) and SW48 KRAS G12A, were observed after exposure to PFOS and PFOA at 2 μM and 10 μM for 7 days. The time and dose-dependent migration phenotype induced by 10 μM PFOS and PFOA was further confirmed by wound healing and trans-well migration assays. To investigate the mechanism of action, derivatization-mass spectrometry-based metabolic profiles were examined from 3D spheroids of SW48 cell lines exposed to PFOS and PFOA (2 μM and 10 μM). Our findings revealed this exposure altered epithelial-mesenchymal transition related metabolic pathways, including fatty acid β-oxidation and synthesis of proteins, nucleotides, and lipids. Furthermore, this phenotype was confirmed by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. These findings show novel insight into the relationship between PFOS, PFOA, and CRC.

中文翻译：

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全氟辛烷磺酸和全氟辛酸促进三维结直肠癌球体迁移

全氟辛烷磺酸 (PFOS) 和全氟辛酸 (PFOA) 是持久性环境污染物，越来越受到全世界公众的关注。然而，人们对它们与结直肠癌 (CRC) 的关系知之甚少。本研究旨在利用一系列生物学技术和代谢谱分析，在体外体外全面研究PFOS和PFOA对CRC发生和进展的影响。在此，在暴露于 2 μM 和 10 μM 的 PFOS 和 PFOA 7 天后，观察到两种 CRC 细胞系 SW48 KRAS 宽型 (WT) 和 SW48 KRAS G12A 的三维 (3D) 球体的迁移。伤口愈合和跨孔迁移测定进一步证实了 10 μM PFOS 和 PFOA 诱导的时间和剂量依赖性迁移表型。为了研究其作用机制，我们对暴露于 PFOS 和 PFOA（2 μM 和 10 μM）的 SW48 细胞系的 3D 球体进行了基于衍生化质谱的代谢谱检查。我们的研究结果表明，这种暴露改变了上皮-间质转化相关的代谢途径，包括脂肪酸β-氧化以及蛋白质、核苷酸和脂质的合成。此外，E-钙粘蛋白的下调以及N-钙粘蛋白和波形蛋白的上调也证实了这种表型。这些发现为 PFOS、PFOA 和 CRC 之间的关系提供了新的见解。