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Int. J. Mol. Sci. 2013, 14(6), 12297-12312; doi:10.3390/ijms140612297

Enhanced Inhibition of Bladder Cancer Cell Growth by Simultaneous Knockdown of Antiapoptotic Bcl-xL and Survivin in Combination with Chemotherapy

Department of Urology, University Hospital "Carl Gustav Carus", Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany
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Received: 22 April 2013 / Revised: 27 May 2013 / Accepted: 5 June 2013 / Published: 7 June 2013
(This article belongs to the Special Issue Molecular Research in Urology)
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Abstract

The overexpression of antiapoptotic genes, such as Bcl-xL and survivin, contributes to the increased survival of tumor cells and to the development of treatment resistances. In the bladder cancer cell lines EJ28 and J82, the siRNA-mediated knockdown of survivin reduces cell proliferation and the inhibition of Bcl-xL sensitizes these cells towards subsequent chemotherapy with mitomycin C and cisplatin. Therefore, the aim of this study was to analyze if the simultaneous knockdown of Bcl-xL and survivin might represent a more powerful treatment option for bladder cancer than the single inhibition of one of these target genes. At 96 h after transfection, reduction in cell viability was stronger after simultaneous inhibition of Bcl-xL and survivin (decrease of 40%–48%) in comparison to the single target treatments (decrease of 29% at best). Furthermore, simultaneous knockdown of Bcl-xL and survivin considerably increased the efficacy of subsequent chemotherapy. For example, cellular viability of EJ28 cells decreased to 6% in consequence of Bcl-xL and survivin inhibition plus cisplatin treatment whereas single target siRNA plus chemotherapy treatments mediated reductions down to 15%–36% only. In conclusion, the combination of simultaneous siRNA-mediated knockdown of antiapoptotic Bcl-xL and survivin—a multitarget molecular-based therapy—and conventional chemotherapy shows great potential for improving bladder cancer treatment.
Keywords: apoptosis; BCL2L1; Bcl-xL; bladder cancer; BIRC5; chemotherapy; combination therapy; RNA interference; siRNA; survivin apoptosis; BCL2L1; Bcl-xL; bladder cancer; BIRC5; chemotherapy; combination therapy; RNA interference; siRNA; survivin
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Kunze, D.; Erdmann, K.; Froehner, M.; Wirth, M.P.; Fuessel, S. Enhanced Inhibition of Bladder Cancer Cell Growth by Simultaneous Knockdown of Antiapoptotic Bcl-xL and Survivin in Combination with Chemotherapy. Int. J. Mol. Sci. 2013, 14, 12297-12312.

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