RT Journal Article SR Electronic T1 Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2901 OP 2912 DO 10.21873/anticanres.15072 VO 41 IS 6 A1 KAZUKI OKUBO A1 MAKOTO ISONO A1 TAKAKO ASANO A1 NINA REßING A1 WOLFGANG A. SCHULZ A1 FINN K. HANSEN A1 AKINORI SATO YR 2021 UL http://ar.iiarjournals.org/content/41/6/2901.abstract AB Background/Aim: Activation of the ubiquitin-proteasome 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 cisplatin-resistant 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.