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金纳米颗粒通过抑制TRAF6/NF-κB诱导的CCL2表达增强胶质瘤细胞的放射敏感性。

Gold nanoparticles enhances radiosensitivity in glioma cells by inhibiting TRAF6/NF-κB induced CCL2 expression.

作者信息

Wang Hao, Xu Qian, Dong Xianning, Guan Zhiling, Wang Ziyu, Hao Yuanyuan, Lu Ruichun, Chen Ling

机构信息

Department of Oncology, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266012, China.

Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266012, China.

出版信息

Heliyon. 2023 Mar 9;9(3):e14362. doi: 10.1016/j.heliyon.2023.e14362. eCollection 2023 Mar.

Abstract

Gliomas are inherently difficult to treat by radiotherapy because glioma cells become radioresistant over time. However, combining radiotherapy with a radiosensitizer could be an effective strategy to mitigate the radioresistance of glioma cells. Gold nanoparticles (AuNPs) have emerged as a promising nanomaterial for cancer therapy, but little is known about whether AuNPs and X-ray radiation have cytotoxic synergistic effects against tumors. In this study, we found that the combination of AuNPs and X-ray irradiation significantly reduced the viabilities, as well as the migration and invasion, of glioma cells. Mechanistically, we observed that the AuNPs inhibited radiation-induced CCL2 expression by inhibiting the TRAF6/NF-κB pathway, which likely manifested the synergistic therapeutic effect between the AuNPs and X-ray radiation. The AuNPs also re-sensitized radioresistant glioma cells by inhibiting CCL2 expression. These results were also observed in another tumor cell line with a different molecular pattern, indicating that the underlying mechanism may be ubiquitous through cancer cells. Lastly, using the glioma mouse model, we observed that AuNPs significantly reduced tumor growth in the presence of X-ray radiation compared to radiotherapy alone.

摘要

胶质瘤本质上很难通过放射疗法进行治疗,因为随着时间的推移,胶质瘤细胞会产生放射抗性。然而,将放射疗法与放射增敏剂相结合可能是减轻胶质瘤细胞放射抗性的有效策略。金纳米颗粒(AuNPs)已成为一种有前景的用于癌症治疗的纳米材料,但关于AuNPs和X射线辐射对肿瘤是否具有细胞毒性协同作用却知之甚少。在本研究中,我们发现AuNPs与X射线照射相结合可显著降低胶质瘤细胞的活力以及迁移和侵袭能力。从机制上讲,我们观察到AuNPs通过抑制TRAF6/NF-κB途径来抑制辐射诱导的CCL2表达,这可能体现了AuNPs与X射线辐射之间的协同治疗效果。AuNPs还通过抑制CCL2表达使放射抗性胶质瘤细胞重新敏感化。在另一种具有不同分子模式的肿瘤细胞系中也观察到了这些结果,这表明潜在机制可能在癌细胞中普遍存在。最后,使用胶质瘤小鼠模型,我们观察到与单独放疗相比,在X射线辐射存在的情况下,AuNPs可显著降低肿瘤生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13f5/10036657/32b1c9eaf359/gr1.jpg

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