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APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy.
Xie, Xuqin; Fan, Chuanwen; Luo, Bin; Zhang, Jing; Jensen, Lasse D; Burman, Jonas; Jönsson, Carolin; Ljusberg, Anna; Larsson, Peter; Zhao, Zengren; Sun, Xiao-Feng.
Afiliación
  • Xie X; Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
  • Fan C; Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
  • Luo B; Department of Gastrointestinal, Bariatric and Metabolic Surgery, Research Center for Nutrition, Metabolism & Food Safety, West China-PUMC C.C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Zhang J; Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • Jensen LD; Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
  • Burman J; Department of Gastrointestinal Surgery, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
  • Jönsson C; Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
  • Ljusberg A; Department of Pathology, the First Hospital of Hebei Medical University, Hebei, China.
  • Larsson P; Department of Health, Medical and Caring Sciences, Linköping University, Linköping, Sweden.
  • Zhao Z; Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
  • Sun XF; Department of Oncology and Department of Biomedical and Clinical Science, Linköping University, Linköping, Sweden.
Mol Cancer Ther ; 22(8): 947-961, 2023 08 01.
Article en En | MEDLINE | ID: mdl-37216282
p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. As there is currently no existing study on combining APR-246 with radiation in rectal cancer, our objective was to investigate whether APR-246 could enhance the sensitivity of colorectal cancer cells, regardless of their p53 status, to radiation treatment. The combination treatment had synergistic effects on HCT116p53-R248W/- (p53Mut) cells, followed by HCT116p53+/+ [wild-type p53 (p53WT)] cells, and exhibited an additive effect on HCT116p53-/- (p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared with p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radiosensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in patients with rectal cancer.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Recto / Neoplasias Colorrectales Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Cancer Ther Asunto de la revista: ANTINEOPLASICOS Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Recto / Neoplasias Colorrectales Tipo de estudio: Diagnostic_studies Límite: Animals / Humans Idioma: En Revista: Mol Cancer Ther Asunto de la revista: ANTINEOPLASICOS Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos