Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou 310018, China; Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Hangzhou 310015, China; College of Quality and Safety Engineering, China Jiliang University, Hangzhou 310018, China.
Institute of Environmental and Health Sciences, China Jiliang University, Hangzhou 310018, China; College of Life Sciences, China Jiliang University, Hangzhou 310018, China.
J Environ Sci (China). 2024 Nov;145:1-12. doi: 10.1016/j.jes.2023.09.031. Epub 2023 Oct 3.
The potential association between colorectal cancer (CRC) and environmental pollutants is worrisome. Previous studies have found that some perfluoroalkyl acids, including perfluorooctane sulfonate (PFOS), induced colorectal tumors in experimental animals and promoted the migration of and invasion by CRC cells in vitro, but the underlying mechanism is unclear. Here, we investigated the effects of PFOS on the proliferation and migration of CRC cells and the potential mechanisms involving activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition (EMT). It was found that PFOS promoted the growth and migration of HCT116 cells at non-cytotoxic concentrations and increased the mRNA expression of the migration-related angiogenic cytokines vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In a mechanistic investigation, the up-stream signal pathway PI3K/Akt-NF-κB was activated by PFOS, and the process was suppressed by LY294002 (PI3K/Akt inhibitor) and BAY11-7082 (NF-κB inhibitor) respectively, leading to less proliferation of HCT116 cells. Furthermore, matrix metalloproteinases (MMP) and EMT-related markers were up-regulated after PFOS exposure, and were also suppressed respectively by LY294002 and BAY11-7082. Moreover, the up-regulation of EMT markers was suppressed by a MMP inhibitor GM6001. Taken together, our results indicated that PFOS promotes colorectal cancer cell migration and proliferation by activating the PI3K/Akt-NF-κB signal pathway and epithelial-mesenchymal transition. This could be a potential toxicological mechanism of PFOS-induced malignant development of colorectal cancer.
结直肠癌（CRC）与环境污染物之间的潜在关联令人担忧。先前的研究发现，某些全氟烷基酸，包括全氟辛烷磺酸（PFOS），在实验动物中诱导结直肠肿瘤，并促进 CRC 细胞在体外的迁移和侵袭，但潜在机制尚不清楚。在这里，我们研究了 PFOS 对 CRC 细胞增殖和迁移的影响及其潜在机制，涉及激活 PI3K/Akt-NF-κB 信号通路和上皮-间充质转化（EMT）。结果发现，PFOS 在非细胞毒性浓度下促进 HCT116 细胞的生长和迁移，并增加迁移相关血管生成细胞因子血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）的 mRNA 表达。在机制研究中，PFOS 激活了上游信号通路 PI3K/Akt-NF-κB，该过程分别被 LY294002（PI3K/Akt 抑制剂）和 BAY11-7082（NF-κB 抑制剂）抑制，导致 HCT116 细胞增殖减少。此外，PFOS 暴露后基质金属蛋白酶（MMP）和 EMT 相关标志物上调，LY294002 和 BAY11-7082 分别抑制这些标志物的表达。此外，MMP 抑制剂 GM6001 抑制 EMT 标志物的上调。总之，我们的研究结果表明，PFOS 通过激活 PI3K/Akt-NF-κB 信号通路和上皮-间充质转化促进结直肠癌细胞的迁移和增殖。这可能是 PFOS 诱导结直肠癌恶性发展的潜在毒理学机制。
