Cisplatin chemotherapy is the standard treatment for metastatic urothelial carcinoma. Although there are second-line chemotherapeutic agents approved by the U.S. Food and Drug Administration (FDA) such as those targeting programmed death-ligand 1 (PD-L1), more effective pharmacotherapy is required for cisplatin-resistant bladder cancer due to its limited overall survival and progression-free survival. The synergistic anti-cancer effect of cisplatin and suberoylanilide hydroxamic acid (SAHA) in cisplatin-resistant bladder cancer cells (T24R2) was examined. Tumor cell proliferation and cell cycle was examined using the cell counting kit (CCK)-8 assays and flow cytometry, respectively. Synergism was examined using the combination index (CI). CCK-8 assay and CI test were used to observe the strong synergistic anti-cancer effect between SAHA and cisplatin. Activation of caspase mediated apoptosis, down-regulated expression of the anti-apoptotic B-cell lymphoma-2 (Bcl-2) and up-regulated expression of pro-apoptotic Bcl-2-associated death promoter (BAD) were observed in Western blot. SAHA synergistically could partially re-sensitize cisplatin-resistant bladder cancer cells (T24R2) through the cell cycle arrest and induction of apoptosis pathway. SAHA-based treatment could be a potential treatment regimen in patients with cisplatin resistant bladder cancer.
Keywords: bladder cancer; cisplatin resistance; suberoylanilide hydroxamic acid.