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Arsenic sulfide enhances radiosensitivity in rhabdomyosarcoma via activating NFATc3-RAG1 mediated DNA double strand break (DSB).
Cai, Yu; Zhu, Chuanying; Lu, Shumin; Kang, Ting; Chen, Shuxian; Feng, Zhuowei; Chen, Siyu.
Afiliación
  • Cai Y; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China.
  • Zhu C; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China.
  • Lu S; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China.
  • Kang T; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China.
  • Chen S; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China.
  • Feng Z; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China.
  • Chen S; Department of Oncology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 200092, Shanghai, China. Electronic address: siyu.chen@shsmu.edu.cn.
Chem Biol Interact ; 399: 111149, 2024 Aug 25.
Article en En | MEDLINE | ID: mdl-39032852
ABSTRACT
Rhabdomyosarcoma (RMS) represents one of the most lethal soft-tissue sarcomas in children. The toxic trace element arsenic has been reported to function as a radiosensitizer in sarcomas. To investigate the role of arsenic sulfide (As4S4) in enhancing radiation sensitization in RMS, this study was conducted to elucidate its underlying mechanism in radiotherapy. The combination of As4S4 and radiotherapy showed significant inhibition in RMS cells, as demonstrated by the cell counting kit-8 (CCK-8) assay and flow cytometry. Subsequently, we demonstrated for the first time that As4S4, as well as the knockdown of NFATc3 led to double-strand break (DSB) through increased expression of RAG1. In vivo experiment confirmed that co-treatment efficiently inhibited RMS growth. Furthermore, survival analysis of a clinical cohort consisting of 59 patients revealed a correlation between NFATc3 and RAG1 expression and overall survival (OS). Cox regression analysis also confirmed the independent prognostic significance of NFATc3 and RAG1.Taken together, As4S4 enhances radiosensitivity in RMS via activating NFATc3-RAG1 mediated DSB. NFATc3 and RAG1 are potential therapeutic targets. As4S4 will hopefully serve as a prospective radio-sensitizing agent for RMS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arsenicales / Tolerancia a Radiación / Rabdomiosarcoma / Sulfuros / Factores de Transcripción NFATC / Roturas del ADN de Doble Cadena Límite: Animals / Child / Female / Humans / Male Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Arsenicales / Tolerancia a Radiación / Rabdomiosarcoma / Sulfuros / Factores de Transcripción NFATC / Roturas del ADN de Doble Cadena Límite: Animals / Child / Female / Humans / Male Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda