Effects of microplastics on chemo-resistance and tumorigenesis of colorectal cancer

IF 8.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Apoptosis Pub Date : 2025-02-09 DOI:10.1007/s10495-025-02085-1
Wen Pan, Yueting Han, Mingqing Zhang, Kegan Zhu, Zhen Yang, Minghan Qiu, Yaoyang Guo, Ziyi Dong, Jie Hao, Xipeng Zhang, Ming Gao, Haiyang Zhang
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Abstract

Microplastics (MPs) are widely distributed environmental pollutants around the world. Although studies have demonstrated that MPs have adverse effects on human health, the relationship between MPs and tumors remains unclear. The gut is the main site of microplastics absorption, and the function of MPs in the chemoresistance and progression of colorectal cancer (CRC) needs more investigation. Here, we show that MPs exist in human CRC tissues for the first time by using a laser direct infrared chemical imaging system. MPs can cause an increase in CRC incidence in animal models and promote resistance to oxaliplatin. It is illustrated that the uptake of MPs enhances levels of autophagy by activating the mTOR pathway. MPs can also promote the disorder of intestinal flora and intestinal inflammation, serving as an essential component in the onset and advancement of CRC. These results indicated that microplastic pollutants in colorectal cancer could mediate protective autophagy through the mTOR/ULK1 axis, which is one of the new reasons for chemo-resistance in CRC under the background of increasingly serious microplastics pollution. This study identified the adverse effects of MPs on colorectal cancer progression and chemotherapy prognosis, and attempted to block the intake of MPs to propose a novel approach for clinical precision treatment.

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微塑料对结直肠癌耐药及肿瘤发生的影响。
微塑料是广泛分布在世界各地的环境污染物。虽然研究表明,MPs对人体健康有不利影响,但MPs与肿瘤之间的关系尚不清楚。肠道是微塑料吸收的主要部位,MPs在结直肠癌(CRC)化疗耐药和进展中的作用有待进一步研究。在这里,我们首次通过激光直接红外化学成像系统发现MPs存在于人类结直肠癌组织中。在动物模型中,MPs可导致CRC发病率增加,并促进对奥沙利铂的耐药性。研究表明,MPs的摄取通过激活mTOR通路来增强自噬水平。MPs还可以促进肠道菌群紊乱和肠道炎症,是CRC发生和发展的重要组成部分。这些结果表明,结直肠癌中微塑料污染物可通过mTOR/ULK1轴介导保护性自噬,这是在微塑料污染日益严重的背景下结直肠癌耐药的新原因之一。本研究明确了MPs对结直肠癌进展和化疗预后的不良影响,并试图阻断MPs的摄入,为临床精准治疗提供新途径。
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来源期刊
Apoptosis
Apoptosis 生物-生化与分子生物学
CiteScore
9.10
自引率
4.20%
发文量
85
审稿时长
1 months
期刊介绍: Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.
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