2. Academic Validation
  3. RNA polymerase I inhibitor CX-5461 suppresses cervical cancer cell growth by inducing DNA damage and mitotic catastrophe and enhances cisplatin sensitivity

RNA polymerase I inhibitor CX-5461 suppresses cervical cancer cell growth by inducing DNA damage and mitotic catastrophe and enhances cisplatin sensitivity

  • Biochem Pharmacol. 2026 Jun:248:117828. doi: 10.1016/j.bcp.2026.117828.
Xiaoli Liu 1,  Ting Xu 2,  Jiaqi Wu 2,  Baokun Zhou 1,  Jinghao Wen 2,  Youzhong Zhang 2,  Baoxia Cui 2,  Cheng-Ming Chiang 3,  Jianli Wang 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 2 Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 3 Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
  • 4 Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: [email protected].
PMID: 41730388 DOI: 10.1016/j.bcp.2026.117828
Abstract

Cervical Cancer is one of the most common malignant tumors among women worldwide. In some regions, its incidence and mortality rates remain high, and patients with HPV-unassociated tumors often have a poor prognosis. Those with advanced or recurrent disease frequently show unsatisfactory treatment outcomes due to metastasis and chemoresistance. Ribosome biogenesis is notably active in various Cancer cells and has emerged as a potential therapeutic target. CX-5461, a specific inhibitor of RNA polymerase I, was investigated in this study for its therapeutic effect and underlying mechanism in cervical Cancer. The results demonstrated that CX-5461 significantly inhibits the proliferation of cervical Cancer cells, activates the ATM/ATR pathway, and induces DNA damage. Furthermore, it leads to abnormal accumulation of Cyclin B1 and aberrant activation of phospho-CDK1-T161, driving cells with DNA damage into Mitosis. This process ultimately triggers mitotic catastrophe, resulting in cell death or senescence. When combined with cisplatin, CX-5461 enhances the sensitivity of cervical Cancer cells to this chemotherapeutic agent. In conclusion, CX-5461 demonstrates potential therapeutic value for cervical Cancer, particularly as a new strategy for patients with primary or platinum-resistant disease.

Keywords

CX-5461; Cell death; Cervical cancer; Cisplatin; DNA damage; Mitotic catastrophe.

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