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微塑料暴露通过调节炎症过程促进皮肤癌细胞的增殖,但抑制正常皮肤细胞的生长。

Microplastics exposure promotes the proliferation of skin cancer cells but inhibits the growth of normal skin cells by regulating the inflammatory process.

机构信息

Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China; Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.

Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.

出版信息

Ecotoxicol Environ Saf. 2023 Nov 15;267:115636. doi: 10.1016/j.ecoenv.2023.115636. Epub 2023 Nov 1.

DOI:10.1016/j.ecoenv.2023.115636
PMID:37918331
Abstract

Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors of the skin, occurring primarily in the elderly population. CSCC is the second most common nonmelanoma skin malignancy in humans. The development of cutaneous squamous cell carcinoma is closely linked to environmental factors. Microplastics, as a new pollutant, are currently being intensively studied for their potential health effects. However, the effect of microplastics on skin cancer is not yet known and is an important scientific question that needs to be addressed. To this end, in the current study, two skin squamous cell carcinoma cell lines (SCL-1 and A431) were utilized to investigate the effects of microplastics on skin cancer, and cell behavior experiments showed that microplastics were internalized into the skin squamous cell carcinoma cell line in a time- and dose-dependent manner. Further experiments showed that microplastics promoted the proliferation of skin cancer cells by MTT, flow cytometry, laser confocal microscopy, Western blotting and other experimental techniques. Mechanistic studies showed that microplastics could lead to increased mitochondrial ROS in skin cancer cells, which in turn caused a change in mitochondrial membrane potential, thus opening mPTP, which in turn caused the release of mt-DNA from mitochondria into the cytoplasm, thus activating NLRP3 and ultimately causing skin cancer cell proliferation. We further evaluated the effect of microplastics on HaCaT cells in a normal skin cell model and showed that microplastics caused damage to normal skin cells through NLRP3-mediated inflammation and scorch death. The current study suggests that microplastics, as a new contaminant, may promote tumor cell proliferation while causing damage to normal skin.

摘要

皮肤鳞状细胞癌(CSCC)是最常见的皮肤恶性肿瘤之一,主要发生在老年人群中。CSCC 是人类第二大常见的非黑色素瘤皮肤恶性肿瘤。皮肤鳞状细胞癌的发生与环境因素密切相关。微塑料作为一种新型污染物,其潜在的健康影响目前正在受到深入研究。然而,微塑料对皮肤癌的影响尚不清楚,这是一个需要解决的重要科学问题。为此,在目前的研究中,我们利用两种皮肤鳞状细胞癌细胞系(SCL-1 和 A431)来研究微塑料对皮肤癌的影响,细胞行为实验表明,微塑料以时间和剂量依赖的方式被内吞进入皮肤鳞状细胞癌细胞系。进一步的实验表明,微塑料通过 MTT、流式细胞术、激光共聚焦显微镜、Western blot 等实验技术促进皮肤癌细胞的增殖。机制研究表明,微塑料可导致皮肤癌细胞中线粒体 ROS 的增加,进而导致线粒体膜电位的改变,从而打开 mPTP,进而导致 mt-DNA 从线粒体释放到细胞质中,从而激活 NLRP3,最终导致皮肤癌细胞增殖。我们进一步在正常皮肤细胞模型中评估了微塑料对 HaCaT 细胞的影响,结果表明微塑料通过 NLRP3 介导的炎症和焦亡对正常皮肤细胞造成损伤。本研究提示,微塑料作为一种新型污染物,可能在促进肿瘤细胞增殖的同时对正常皮肤造成损伤。

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