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Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents

Oncogene volume 27, pages 55–62 (2008)Cite this article

Abstract

Recently, we reported prognostic significance of thromboxane synthase (TXAS) gene expression in invasive bladder cancer. The positive correlation between elevated TXAS expression and shorter patient survival supports a potential role for TXAS-regulated pathways in tumor metastases. In this study, using immunohistochemical analysis, we found an increased expression of TXAS protein in bladder cancer. Treatment of T24 and transitional cell carcinoma TCC-SUP bladder cancer cells with the TXAS inhibitors furegrelate or ozagrel induced an apoptotic effect measured as an increase in caspase-3 activation and cell death, and decreased survivin expression. Pharmacological inhibition of TXAS using the TXAS inhibitor furegrelate increased sensitivity to the chemotherapeutic agents cisplatin and paclitaxel. Molecular inhibition of TXAS expression by siRNA significantly decreased cell growth and migration. In concordance with the pharmacological data, siRNA-mediated reduction of TXAS expression increased sensitivity to cisplatin and paclitaxel in T24 and TCC-SUP cells. In summary, the data support a role for the thromboxane A2 pathway in the pathogenesis of bladder cancer and the potential utility of modulation of this signaling pathway for cancer chemotherapy.

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Acknowledgements

We acknowledge the technical assistance of Alex McPherson, Margaret Romano (Hollings Cancer Center Tumor Bank) and Rick Peppler (Flow Cytometry Facility).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA

    O Moussa, J M Riker, J Klein, M Fraig & D K Watson

  2. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA

    O Moussa, J M Riker, J Klein & D K Watson

  3. Departments of Pharmacology and Medicine, Medical University of South Carolina, Charleston, SC, USA

    P V Halushka

  4. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA

    D K Watson

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  1. O Moussa
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  2. J M Riker
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Correspondence to O Moussa.

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Moussa, O., Riker, J., Klein, J. et al. Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents. Oncogene 27, 55–62 (2008). https://doi.org/10.1038/sj.onc.1210629

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  • DOI: https://doi.org/10.1038/sj.onc.1210629

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