The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma

The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma

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Urothelial carcinoma (UC) comprises the majority of bladder cancers.Standard platinum-based chemotherapy has a response rate of approximately 50%, but drug resistance develops after short-term treatment.Deubiquitinating (DUB) enzyme inhibitors increase protein polyubiquitination and endoplasmic reticulum (ER) stress, which might further suppress cancer Fan Shop - Oilers - Jerseys stemness and overcome cisplatin resistance.Therefore, we investigated the cytotoxic effect and potential mechanisms of b-AP15 on urothelial carcinoma.Our results revealed that b-AP15 induced ER stress and apoptosis in BFTC905, T24, T24/R (cisplatin-resistant), and RT4 urothelial carcinoma cell lines.

Inhibition of the MYC signaling pathway and cancer stemness by b-AP15 was confirmed by RNA sequencing, RT-PCR, immunoblotting, and sphere-forming assays.In the mouse xenograft model, the combination of b-AP15 Nut Butters and cisplatin showed superior therapeutic effects compared with either monotherapy.