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Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells
Kazuki Okubo1, Makoto Isono1, Takako Asano1
1Department of Urology, National Defense Medical College, Tokorozawa, Japan.
Anticancer Research
|June 4, 2021
Summary
Targeting the ubiquitin-proteasome system (UPS) may overcome cisplatin resistance in bladder cancer. UPS-targeting drugs showed increased efficacy in resistant cells, suggesting a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The ubiquitin-proteasome system (UPS) is implicated in cancer drug resistance.
- Understanding UPS activation in bladder cancer is crucial for developing new treatments.
Purpose of the Study:
- To investigate the link between UPS activation and cisplatin resistance in bladder cancer cells.
- To evaluate the effectiveness of UPS-targeting drugs in overcoming cisplatin resistance.
Main Methods:
- Established cisplatin-resistant bladder cancer cell lines (J82-cisR, T24-cisR).
- Assessed UPS activation status in resistant versus parental cells.
- Tested the efficacy of UPS inhibitors (MLN7243, oprozomib, ixazomib, RTS-V5).
Main Results:
- UPS was significantly activated in cisplatin-resistant bladder cancer cells.
- UPS inhibitors demonstrated enhanced efficacy in inducing apoptosis and inhibiting growth in resistant cells.
- UPS inhibitors triggered endoplasmic reticulum stress at lower concentrations in resistant cells.
Conclusions:
- Targeting the ubiquitin-proteasome system presents a promising therapeutic strategy for cisplatin-resistant bladder cancer.
- UPS inhibition may sensitize resistant bladder cancer cells to treatment.
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