Exposure to low dose ZnO nanoparticles induces hyperproliferation and malignant transformation through activating the CXCR2/NF-kappa B/ STAT3/ERK and AKT pathways in colonic mucosal cells
Exposure to low dose ZnO nanoparticles induces hyperproliferation and malignant transformation through activating the CXCR2/NF-kappa B/ STAT3/ERK and AKT pathways in colonic mucosal cells
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暴露于低剂量 ZnO 纳米粒子可通过激活结肠粘膜细胞中的 CXCR2/NF-kappa B/ STAT3/ERK 和 AKT 途径诱导过度增殖和恶性转化
DOI：
10.1016/j.envpol.2020.114578
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Cui Shuxiang
中科院分区：
文献类型：
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作者：
Meng Jian;Zhou Xiaoling;Yang Juan;Qu Xianjun;Cui Shuxiang
随着纳米氧化锌在众多领域的应用，其对人体健康的生物学风险也值得关注。ZnO纳米颗粒是否具有风险以及结肠细胞如何对入侵的ZnO纳米颗粒做出反应仍然是未知的。本研究通过体外和体内两种方法评价了ZnO纳米粒对结肠黏膜细胞的生物学效应。APC突变但表型正常的IMCE细胞经ZnO NPs处理24 h后，通过激活CXCR 2/NF-κB/STAT 3/ERK和AKT通路而表现出过度增殖。长期暴露于ZnO纳米颗粒可导致IMCE细胞发生恶性转化，表现为形态学改变，细胞生长能力不依赖于贴壁生长。重要的是，暴露于ZnO纳米颗粒的IMCE细胞在裸鼠皮下生长并诱导肿瘤发生。结论：ZnO纳米颗粒可通过CXCR 2/NF-κB/STAT 3/ERK和AKT途径诱导结肠黏膜细胞恶性转化。我们建议有必要考虑对胃肠道接触纳米材料使用预防原则。
As ZnO nanoparticles have been applied in many fields, their biological risks on human health, of course, are worthy of our attention. Whether ZnO NPs have the risk and how colonic cells respond to the invaded ZnO NPs are still unknown. Herein, we evaluated the biological effects of ZnO NPs on colonic mucosal cells by in vitro andin vivomethods. IMCE cells, withAPCmutation but phenotypically normal, demonstrated hyperproliferation through activating the CXCR2/NF-κB/STAT3/ERK and AKT pathways when exposed to ZnO NPs for 24 h. Long-term exposure of ZnO NPs resulted in the malignant transformation of IMCE cells, showing the morphological changes, anchorage-independent cell growth ability. Importantly, IMCE cells exposed to ZnO NPs subcutaneously grew and induced tumorigenesis in nude mice. In conclusion, exposure of ZnO NPs could induce malignant transformation of colonic mucosal cells through the CXCR2/NF-κB/STAT3/ERK and AKT pathways. We suggest that it was necessary to consider using the precautionary principle for gastrointestinal contact nanomaterials.