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Targeting ABCA1 via Extracellular Vesicle-Encapsulated Staurosporine as a Therapeutic Strategy to Enhance Radiosensitivity.
Yang, Qi; Gao, Wenyan; Li, Xinyue; Li, Xin; Zhou, Xuantong; Li, Wenxin; Zhou, Changchun; Luo, Aiping; Liu, Zhihua.
Afiliação
  • Yang Q; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Gao W; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Li X; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Li X; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Zhou X; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • Li W; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Zhou C; Biobank, Cancer Research Center, Shandong Cancer Hospital, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China.
  • Luo A; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • Liu Z; State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Adv Healthc Mater ; 13(16): e2400381, 2024 06.
Article em En | MEDLINE | ID: mdl-38467587
ABSTRACT
Cancer stem cells (CSCs) are essential for tumor initiation, recurrence, metastasis, and resistance. However, targeting CSCs as a therapeutic approach remains challenging. Here, a stemness signature based on 22-gene is developed to predict prognosis in esophageal squamous cell carcinoma (ESCC). Staurosporine (STS) is identified as a radioresistance suppressor by high-throughput screening of a library of 2131 natural compounds, leading to dramatically improved radiotherapy efficacy in subcutaneous tumor models. Mechanistically, STS inhibits cell proliferation through the mTOR/AKT signaling pathway and suppressed stemness by targeting ATP-binding cassette A1 (ABCA1), which is transcriptionally regulated by liver X receptor alpha (LXRα). STS can selectively bind to the nucleotide-binding domain (NBD) of ABCA1 and compete for ATP, blocking ABCA1-mediated drug efflux and facilitating intracellular accumulation of STS. Considering the cytotoxicity of STS, an extracellular vesicle-encapsulated STS system (EV-STS) is established for effective STS delivery. EV-STS shows remarkable tumor growth inhibition, even at half the dose of STS, with superior safety and efficacy. These findings indicate that ABCA1 may serve as a predictor of response to neoadjuvant chemotherapy and/or radiotherapy in ESCC patients. EV-STS has shown improved antitumor efficacy and low systemic toxicity, offering a promising therapeutic approach for ESCC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tolerância a Radiação / Estaurosporina / Transportador 1 de Cassete de Ligação de ATP / Vesículas Extracelulares Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tolerância a Radiação / Estaurosporina / Transportador 1 de Cassete de Ligação de ATP / Vesículas Extracelulares Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China