RCC1 knockdown sensitizes drug-resistant colorectal cancer to 5-fluorouracil or doxorubicin by impairing DNA repair
Rattachement africain : mo, cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Aim: This study aimed to elucidate the role of regulator of chromosome condensation 1 (RCC1) in colorectal cancer (CRC) progression, as well as its involvement in chemoresistance. We specifically examined how RCC1 knockdown modulates cellular responses, including cell cycle, apoptosis, and senescence induced by 5-fluorouracil (5-FU) or doxorubicin (Doxo) in both parental and drug-resistant CRC cell lines. Additionally, we assessed the potential of RCC1 inhibition as an adjuvant therapeutic strategy to enhance the efficacy of chemoradiotherapy in CRC. Methods: The expression of RCC1 in colon cancer tissues and corresponding adjacent non-cancerous tissues was evaluated through tissue microarrays, and its correlation with characteristics and patient prognosis was also examined. Subsequently, a series of in vivo and in vitro experiments based on parental and drug-resistant CRC cell lines were conducted to assess the impact of RCC1 knockdown on sensitivity to 5-FU or Doxo. Finally, transcriptomic analysis and subsequent validation assays were performed to explore the underlying molecular mechanisms. Results: RCC1 knockdown significantly enhanced the antitumor efficacy of 5-FU and Doxo in both CRC and drug-resistant CRC cells. In xenograft models, RCC1 knockdown in combination with 5-FU or Doxo suppressed tumor growth with no evident systemic toxicity observed. Transcriptomic profiling and experimental verification revealed that RCC1 knockdown may impair DNA repair by downregulating key repair proteins, thereby leading to more severe and sustained DNA damage. Conclusion: Our results indicate that RCC1 downregulation enhances the responsiveness of both parental and drug-resistant CRC cells to 5-FU and Doxo, highlighting its potential as a therapeutic adjunct to improve clinical outcomes in CRC.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- RCC1 knockdown sensitizes drug-resistant colorectal cancer to 5-fluorouracil or doxorubicin by impairing DNA repair
- Date Crossref
- 10/11/2025
- Éditeur
- OAE Publishing Inc.
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
University of Macau MoE Frontiers Science Center for Precision Oncology pays non établi dans la noticeUniversité ou école supérieure
-
Zhuhai People's Hospital Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment pays non établi dans la noticeÉtablissement de santé
-
Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine pays non établi dans la noticeÉtablissement de santé
-
Zhuhai Institute of Advanced Technology pays non établi dans la noticeStructure de recherche
-
Faculty of Health Sciences Cancer Centre pays non établi dans la noticeUniversité ou école supérieure
-
Clinical Center for Immunology and Gut Microecology pays non établi dans la noticeÉtablissement de santé
MoE Frontiers Science Center for Precision Oncology — University of Macau, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment — Zhuhai People's Hospital et Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.