DMC-siERCC2 hybrid nanoparticle enhances TRAIL sensitivity by inducing cell cycle arrest for glioblastoma treatment.

Autor: Song M; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China; Technology School of Medicine, The South China University, Guangzhou, Guangdong 510000, China., Wang T; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China; School of Pharmaceutical Sciences, Dali University, Dali, Yunnan 671000, China., Liu T; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China; School of Pharmaceutical Sciences, Dali University, Dali, Yunnan 671000, China., Lei T; School of Pharmaceutical Sciences, Dali University, Dali, Yunnan 671000, China., Teng X; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China., Peng Q; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China., Zhu Q; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China., Chen F; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China; School of Pharmaceutical Sciences, Dali University, Dali, Yunnan 671000, China., Zhao G; Department of Pathology, Jilin Medical University, Jilin, Jilin 130013, China., Li K; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China. Electronic address: kaishu_li@126.com., Qi L; Division of Gastroenterology, Institute of Digestive Disease, Qingyuan People's Hospital, the Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511518, China. Electronic address: qiling1718@gzhmu.edu.cn.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 May; Vol. 174, pp. 116470. Date of Electronic Publication: 2024 Apr 01.
DOI: 10.1016/j.biopha.2024.116470
Abstrakt: ERCC2 plays a pivotal role in DNA damage repair, however, its specific function in cancer remains elusive. In this study, we made a significant breakthrough by discovering a substantial upregulation of ERCC2 expression in glioblastoma (GBM) tumor tissue. Moreover, elevated levels of ERCC2 expression were closely associated with poor prognosis. Further investigation into the effects of ERCC2 on GBM revealed that suppressing its expression significantly inhibited malignant growth and migration of GBM cells, while overexpression of ERCC2 promoted tumor cell growth. Through mechanistic studies, we elucidated that inhibiting ERCC2 led to cell cycle arrest in the G0/G1 phase by blocking the CDK2/CDK4/CDK6/Cyclin D1/Cyclin D3 pathway. Notably, we also discovered a direct link between ERCC2 and CDK4, a critical protein in cell cycle regulation. Additionally, we explored the potential of TRAIL, a low-toxicity death ligand cytokine with anticancer properties. Despite the typical resistance of GBM cells to TRAIL, tumor cells undergoing cell cycle arrest exhibited significantly enhanced sensitivity to TRAIL. Therefore, we devised a combination strategy, employing TRAIL with the nanoparticle DMC-siERCC2, which effectively suppressed the GBM cell proliferation and induced apoptosis. In summary, our study suggests that targeting ERCC2 holds promise as a therapeutic approach to GBM treatment.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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