pevonedistat has been researched along with Carcinoma--Transitional-Cell* in 2 studies
2 other study(ies) available for pevonedistat and Carcinoma--Transitional-Cell
| Article | Year |
|---|---|
Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells.
Topics: Antigens, Differentiation; Apoptosis; Arsenites; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell Proliferation; Cisplatin; Humans; SOXB1 Transcription Factors; Urinary Bladder Neoplasms | 2023 |
MLN4924 Synergistically Enhances Cisplatin-induced Cytotoxicity via JNK and Bcl-xL Pathways in Human Urothelial Carcinoma.
Cisplatin-based chemotherapy is the primary treatment for metastatic bladder urothelial carcinoma. However, the response rate is only 40-65%. This study investigated the anti-tumor effect and underlying mechanisms of the combination of cisplatin and the NEDD8-activating enzyme inhibitor MLN4924 in human bladder urothelial carcinoma. The combination of cisplatin and MLN4924 exerted synergistic cytotoxicity on two high-grade bladder urothelial carcinoma cell lines, NTUB1 and T24 (combination index <1). MLN4924 also potentiated the cisplatin-induced apoptosis and activation of caspase-3 and -7, phospho-histone H2A.X and PARP. c-Jun N-terminal kinase (JNK) activation and a down-regulation of B-cell lymphoma-extra large (Bcl-xL) were also observed during cisplatin and MLN4924 treatment. Inhibition of JNK activation partially restored cell viability and Bcl-xL expression. Bcl-xL overexpression also rescued cell viability. MLN4924 significantly potentiated cisplatin-induced tumor suppression in urothelial carcinoma xenograft mice. In summary, MLN4924 synergistically enhanced the anti-tumor effect of cisplatin via an increase in DNA damage, JNK activation and down-regulation of Bcl-xL in urothelial carcinoma cells. These findings provide a new therapeutic strategy for the treatment of bladder cancer. Topics: Animals; Antineoplastic Agents; Apoptosis; bcl-X Protein; Carcinoma, Transitional Cell; Caspase 3; Caspase 7; Cell Line, Tumor; Cisplatin; Cyclopentanes; Drug Combinations; Drug Synergism; Gene Expression Regulation, Neoplastic; Histones; Humans; MAP Kinase Kinase 4; Mice; Mice, Nude; NEDD8 Protein; Neoplasm Grading; Poly(ADP-ribose) Polymerases; Pyrimidines; Signal Transduction; Ubiquitins; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays | 2015 |