Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells
Ubiquitin-proteasome System Is a Promising Target for Killing Cisplatin-resistant Bladder Cancer Cells
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DOI：
10.21873/anticanres.15072
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发表时间：
2021-06
影响因子：
2
通讯作者：
K. Okubo;M. Isono;T. Asano;Nina Reßing;W. Schulz;F. Hansen;A. Sato
中科院分区：
文献类型：
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作者：
K. Okubo;M. Isono;T. Asano;Nina Reßing;W. Schulz;F. Hansen;A. Sato
背景/目的：泛素-蛋白酶体系统（UPS）的激活已被证明与癌症的耐药性有关。使用膀胱癌细胞，我们研究了UPS激活和顺铂耐药性之间的关联，以及UPS靶向药物的疗效。材料与方法：我们建立了顺铂耐药膀胱癌细胞（J82-cisR、T24-cisR），并检查了UPS的激活状态以及MLN 7243、奥普佐米、ixazomib和RTS-V5的疗效。结果：顺铂耐药膀胱癌细胞的UPS与其亲本对照相比被激活。所有的UPS靶向药物诱导凋亡和抑制生长更有效地在顺铂耐药的膀胱癌细胞比他们在父母的控制。此外，这些UPS靶向药物通过在顺铂耐药膀胱癌细胞中以较低浓度引起未折叠蛋白积累来诱导内质网应激。结论：靶向UPS可能是治疗顺铂耐药膀胱癌的有效策略。
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.