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

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

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Received: 22 April 2013; in revised form: 27 May 2013 / Accepted: 5 June 2013 / Published: 7 June 2013
(This article belongs to the Special Issue Molecular Research in Urology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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
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MDPI and ACS Style

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.

AMA Style

Kunze D, Erdmann K, Froehner M, Wirth MP, Fuessel S. Enhanced Inhibition of Bladder Cancer Cell Growth by Simultaneous Knockdown of Antiapoptotic Bcl-xL and Survivin in Combination with Chemotherapy. International Journal of Molecular Sciences. 2013; 14(6):12297-12312.

Chicago/Turabian Style

Kunze, Doreen; Erdmann, Kati; Froehner, Michael; Wirth, Manfred P.; Fuessel, Susanne. 2013. "Enhanced Inhibition of Bladder Cancer Cell Growth by Simultaneous Knockdown of Antiapoptotic Bcl-xL and Survivin in Combination with Chemotherapy." Int. J. Mol. Sci. 14, no. 6: 12297-12312.


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