Chemosensitization of bladder cancer cells by survivin-directed antisense oligodeoxynucleotides and siRNA.
Survivin is known to be overexpressed in numerous tumor types including human bladder cancer and to cause resistance to radiation and chemotherapy. Therefore, we tested the antisense oligodeoxynucleotide AS-SVV286 and the small interfering RNA si-SVV284 to down-regulate survivin in the BCa cell lines EJ28 and 5637 thereby acting as sensitizers for chemotherapy. Pretreatment with these inhibitors followed by chemotherapy caused an enhanced decrease in cell viability. The observed reduction in cell counts associated with increased rates of apoptosis paralleled the degree of reduction of survivin expression that was achieved more efficiently by the siRNA than by the AS-ODN. Nevertheless, both therapy approaches in combination with all tested chemotherapeutics provoked a remarkable inhibition of viability and may serve as suitable additive tools for chemosensitization of bladder cancer cells.
Fuessel
Susanne
S
Department of Urology, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden, Germany. susanne.fuessel@uniklinikum-dresden.de
Herrmann
Jana
J
Ning
Shuangli
S
Kotzsch
Matthias
M
Kraemer
Kai
K
Schmidt
Uta
U
Hakenberg
Oliver W
OW
Wirth
Manfred P
MP
Meye
Axel
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D000077022:Survivin; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D034741:RNA, Small Interfering; D000077022:Survivin