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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
PubMed
Abstract

Insights

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.
Keywords:
Ubiquitin-proteasome systemcisplatin-resistant bladder cancerendoplasmic reticulum stress

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