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Konac E, Varol N, Kiliccioglu I, et al. Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells. Oncol Lett. 2015;10(1):560-564doi: 10.3892/ol.2015.3250.
Konac, E., Varol, N., Kiliccioglu, I., & Bilen, C. Y. (2015). Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells. Oncology letters, 10(1), 560-564. https://doi.org/10.3892/ol.2015.3250
Konac, Ece, et al. "Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells." Oncology letters vol. 10,1 (2015): 560-564. doi: https://doi.org/10.3892/ol.2015.3250
Konac E, Varol N, Kiliccioglu I, Bilen CY. Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells. Oncol Lett. 2015 Jul;10(1):560-564. doi: 10.3892/ol.2015.3250. Epub 2015 May 20. PMID: 26171069; PMCID: PMC4487089.
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Oncol Lett. 2015 Jul;10(1):560-564. doi: 10.3892/ol.2015.3250. Epub 2015 May 20.

Synergistic effects of cisplatin and proteasome inhibitor bortezomib on human bladder cancer cells.

Oncology letters

Ece Konac, Nuray Varol, Ilker Kiliccioglu, Cenk Y Bilen

Affiliations

  1. Department of Medical Biology and Genetics, Faculty of Medicine, Gazi University, Ankara 06500, Turkey.
  2. Department of Urology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.

PMID: 26171069 PMCID: PMC4487089 DOI: 10.3892/ol.2015.3250

Abstract

The proteasome inhibitor bortezomib is a promising novel agent in bladder cancer therapy; however, inducible cytoprotective mechanisms may limit its potential efficacy. To date, the cellular and molecular effects of proteasome inhibitors on bladder cancer cells have been poorly characterized. Despite the consistent rate of initial responses, cisplatin treatment typically results in the development of chemoresistance, leading to therapeutic failure. Therefore, the present study aimed to characterize the molecular mechanisms underlying the anti-proliferative effects of cisplatin and bortezomib combination therapy on the human T24 bladder cancer cell line, by analyzing the protein expression levels of apoptotic genes. Cytotoxic effects were measured using a water-soluble tetrazolium salt-1 assay, and the apoptosis-associated molecules were examined using western blot analysis and ELISA. It was observed that combined administration of cisplatin and bortezomib induced upregulation of caspase-3, -8 and -9, B-cell lymphoma-2 (Bcl-2)-like 11 and Bcl-2-interacting killer, but downregulated Bcl-2 and Bcl-extra large protein expression levels in T24 cells in a dose-dependent manner. Furthermore, enhanced protein expression of caspase-8 and -9, in line with the significantly increased caspase-3 activation, was detected when the cells were treated with a combination of cisplatin and bortezomib, compared with that of either agent alone. Bortezomib appeared to synergize with cisplatin to promote apoptosis via the extrinsic and intrinsic apoptotic pathways. Taken together, the results of the current study provide the preclinical framework for additional evaluation of the effects of combining bortezomib with other agents to induce apoptosis in bladder cancer cells.

Keywords: apoptosis; bladder cancer cells; bortezomib; cisplatin

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