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Updated: Aug 23, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Vitamin D3 sensitizes resistant human bladder cancer cells to cisplatin by regulating Sirtuin 1 gene expression
1Department of Urology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, China. hqyysongjing@163.com.
Objective:
Cisplatin is a standard chemotherapeutic agent for advanced bladder cancer, but its efficacy is limited due to drug resistance. Vitamin D3 may reverse cancer multidrug resistance, but the potential molecular mechanisms are still only partially known. The purpose of this study was to explore the mechanism by which vitamin D3 reverses cisplatin resistance in bladder cancer to improve therapeutic efficacy and ameliorate the prognosis of cisplatin-resistant bladder cancer.
Patients And Methods:
The levels of vitamin D3 and sirtuin 1 protein were detected in cisplatin-resistant bladder cancer patients and cisplatin-sensitive patients. The cisplatin-resistant bladder cancer cell lines T24/DDP and UMUC3R were used as cell experimental models, and the migration, apoptosis, mitochondrial reactive oxygen species accumulation and autophagy of cells were assessed in the present study.
Results:
Vitamin D3 levels were decreased, and sirtuin 1 protein levels were increased in cisplatin-resistant bladder cancer patients compared with cisplatin-sensitive bladder cancer patients. Vitamin D3 treatment markedly repressed sirtuin 1 expression, and overexpression of the sirtuin 1 gene led to mitochondrial reactive oxygen species generation, promoted the initiation of autophagosome formation and enhanced autophagic flux. Cisplatin treatment in the presence of vitamin D3 inhibited cell invasion and migration and induced apoptosis and enhancing the sirtuin 1 gene abolished the effect of vitamin D3 by regulating mitochondrial reactive oxygen species accumulation and autophagosome formation.
Conclusions:
These data support a mechanism wherein the sirtuin 1 gene plays a crucial role in vitamin D3 reversing cisplatin resistance in bladder cancer and may provide useful preventive and therapeutic applications in the future.
Insights
Vitamin D3 reverses cisplatin resistance in bladder cancer by repressing sirtuin 1 (SIRT1). This mechanism involves regulating mitochondrial reactive oxygen species and autophagy, offering potential therapeutic strategies for bladder cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cisplatin is a cornerstone chemotherapy for advanced bladder cancer, yet drug resistance significantly curtails its effectiveness.
- The potential of Vitamin D3 to overcome multidrug resistance in cancer is recognized, but its precise molecular underpinnings remain incompletely elucidated.
- Understanding these mechanisms is crucial for enhancing therapeutic outcomes in cisplatin-resistant bladder cancer.
Purpose of the Study:
- To investigate the molecular mechanism by which Vitamin D3 reverses cisplatin resistance in bladder cancer.
- To identify key molecular players involved in Vitamin D3's action against cisplatin-resistant bladder cancer cells.
- To provide a basis for improving the efficacy of cisplatin-based chemotherapy and the prognosis of patients with resistant bladder cancer.
Main Methods:
- Comparative analysis of Vitamin D3 and sirtuin 1 (SIRT1) protein levels in cisplatin-resistant versus cisplatin-sensitive bladder cancer patients.
- Utilizing cisplatin-resistant bladder cancer cell lines (T24/DDP and UMUC3R) as experimental models.
- Assessing cellular processes including migration, apoptosis, mitochondrial reactive oxygen species (ROS) generation, and autophagy.
Main Results:
- Cisplatin-resistant bladder cancer patients exhibited lower Vitamin D3 levels and higher SIRT1 protein levels compared to sensitive patients.
- Vitamin D3 treatment significantly suppressed SIRT1 expression.
- SIRT1 overexpression induced mitochondrial ROS, promoted autophagosome formation, and enhanced autophagic flux. Conversely, Vitamin D3 combined with cisplatin inhibited cell invasion and migration while inducing apoptosis.
- Restoring SIRT1 expression counteracted Vitamin D3's beneficial effects by modulating ROS and autophagy.
Conclusions:
- The sirtuin 1 (SIRT1) gene is a critical mediator in Vitamin D3's ability to overcome cisplatin resistance in bladder cancer.
- These findings highlight a novel therapeutic pathway involving Vitamin D3 and SIRT1 modulation.
- The study suggests potential future applications for preventive and therapeutic strategies against cisplatin-resistant bladder cancer.
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