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Sie sind hier: Startseite AK Hansen Publikationen Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells

KAZUKI OKUBO, MAKOTO ISONO, TAKAKO ASANO, NINA REßING, WOLFGANG A SCHULZ, FINN K HANSEN, and AKINORI SATO (2021)

Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells

Anticancer Research, 41(6):2901–2912.

Background/Aim: Activation of the ubiquitinproteasome system (UPS) has been shown to be associated with drug resistance in cancer. Using bladder cancer cells, we investigated the association between UPS activation and cisplatin resistance and also the efficacy of UPS-targeting drugs. Materials and Methods: We established cisplatinresistant bladder cancer cells (J82-cisR, T24-cisR) and examined the activation status of the UPS and the efficacy of MLN7243, oprozomib, ixazomib, and RTS-V5. Results: The UPS in cisplatin-resistant bladder cancer cells was activated compared to that in their parental controls. All the UPS-targeting drugs induced apoptosis and inhibited growth more effectively in the cisplatin-resistant bladder cancer cells than they did in the parental controls. Furthermore, these UPS-targeting drugs induced endoplasmic reticulum stress by causing unfolded protein accumulation at lower concentrations in the cisplatin-resistant bladder cancer cells. Conclusion: Targeting the UPS could be an effective strategy for treating cisplatin-resistant bladder cancer.

Cisplatin-resistant bladder cancer, Endoplasmic reticulum stress, Ubiquitin-proteasome system