Characterization and treatment of gemcitabine- and cisplatin-resistant bladder cancer cells with a pan-RAS inhibitor.

Autor: Yoshino H; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Yokoyama S; Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Tamai M; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Okamura S; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Iizasa S; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Sakaguchi T; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Osako Y; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Inoguchi S; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Matsushita R; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Yamada Y; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Nakagawa M; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Tatarano S; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Tanimoto A; Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan., Enokida H; Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
Jazyk: angličtina
Zdroj: FEBS open bio [FEBS Open Bio] 2023 Jun; Vol. 13 (6), pp. 1056-1066. Date of Electronic Publication: 2023 Apr 29.
DOI: 10.1002/2211-5463.13616
Abstrakt: Combination chemotherapy with gemcitabine and cisplatin (GC) is recommended as the primary treatment for advanced bladder cancer (BC). However, the benefits of this approach are limited owing to the acquisition of drug resistance. Here, we found that gemcitabine-resistant and cisplatin-resistant BCs do not exhibit cross-resistance, and that these BCs exhibit different mRNA patterns, as revealed using RNA sequence analysis. To overcome drug resistance, we used the newly developed pan-RAS inhibitor Compound 3144. Compound 3144 inhibited cell viability through suppression of RAS-dependent signaling in gemcitabine- and cisplatin-resistant BCs. RNA sequencing revealed that several genes and pathways, particularly those related to the cell cycle, were significantly downregulated in Compound 3144-treated BCs. These findings provide insights into potential therapeutic strategies for treating BC.
(© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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