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| Content Provider | MDPI |
|---|---|
| Author | Kunze, Doreen Erdmann, Kati Froehner, Michael Wirth, Manfred Fuessel, Susanne |
| 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. |
| File Size | 433152 |
| Ending Page | 12312 |
| Page Count | 16 |
| Starting Page | 12297 |
| File Format | |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms140612297 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 6 |
| Volume Number | 14 |
| Language | English |
| Publisher Date | 2013-06-07 |
| Access Restriction | Open |
| Subject Keyword | apoptosis BCL2L1 Bcl-xL bladder cancer BIRC5 chemotherapy combination therapy RNA interference siRNA survivin |
| Content Type | Text |
| Resource Type | Article |
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