siRNA-mediated inhibition of antiapoptotic genes enhances chemotherapy efficacy in bladder cancer cells.
BACKGROUND
The up-regulation of antiapoptotic B-cell CLL/lymphoma 2 (BCL2), BCL2-like 1 (BCLXL), X-linked inhibitor of apoptosis (XIAP) and survivin is one mechanism by which cancer cells develop resistance towards chemotherapeutics. Therefore, the knockdown of these four genes could sensitise bladder cancer (BCa) cells towards chemotherapy.


METHODS
BCL2, BCLXL, XIAP and survivin were inhibited using siRNAs--either one target-alone or all four targets simultaneously--in EJ28 and J82 BCa cells. After 24 h, cells were treated with mitomycin C or cisplatin. Treatment effects were analysed regarding cell viability, cell count and apoptosis induction.


RESULTS
Knockdown of BCLXL and survivin, as well as the simultaneous inhibition of all four antiapoptotic genes, sensitised EJ28 and J82 cells towards mitomycin C and cisplatin.


CONCLUSIONS
Since the contribution of one antiapoptotic gene to chemotherapy response can vary between BCa cell lines, the simultaneous knockdown of multiple inhibitors of apoptosis might represent a more promising option for enhancing chemotherapy efficacy in BCa treatment.
Department of Urology, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. Doreen.Kunze@uniklinikum-dresden.de
Doreen
D
Kunze
Kati
K
Erdmann
Michael
M
Froehner
Manfred P
MP
Wirth
Susanne
S
Fuessel
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D020868:Gene Silencing; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016685:Mitomycin / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000235:genetics; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051020:bcl-X Protein; D016685:Mitomycin; D002945:Cisplatin