Introduction of a survivin gene-specific small inhibitory RNA inhibits growth of pancreatic cancer cells.
BACKGROUND
The anti-apoptotic molecule survivin is expressed in human cancers of various origins. Since this molecule possesses multiple functions, including apoptosis inhibition, cell cycle promotion and enhancement of Fas ligand expression, survivin has attracted growing attention as a target in cancer treatment. A survivin-specific small inhibitory RNA (siRNA) was introduced into pancreatic cancer cells to investigate its effect on cancer cell growth.


METHODS
Survivin mRNA and protein expression were examined by RT-PCR and Western blotting, respectively. DNA histogram analysis was performed using a flow cytometer.


RESULTS
The introduction of survivin-specific siRNA reduced survivin mRNA and protein expression in PANC-1 cells by over 90% and to an undetected amount, respectively, and induced growth inhibition. The siRNA transfectants showed pronounced morphological changes including enlargement of cells and multinucleation. siRNA transfectants did not show cell cycle arrest, but underwent apoptosis.


CONCLUSIONS
Our data suggest that the use of survivin-specific siRNA deserves further investigation as a novel approach to cancer therapy.
Tsuji
Naoki
N
Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Asanuma
Koichi
K
Kobayashi
Daisuke
D
Yagihashi
Atsuhito
A
Watanabe
Naoki
N
D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D000077022:Survivin; D014162:Transfection
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin