Targeting of CDC20 via small interfering RNA causes enhancement of the cytotoxicity of chemoradiation.
BACKGROUND
Cell division cycle 20 homologue (CDC20), which encodes a protein that promotes chromosomal separation, is highly expressed in several carcinomas, including pancreatic cancer.


METHODS
To ascertain whether this gene could be a potential therapeutic target, the RNA interference technique was applied using small interfering RNA (siRNA) to knockdown CDC20 expression.


RESULTS
The CDC20 siRNA showed more than 90% inhibition of CDC20 expression at both the transcriptional and translational levels and the specific knockdown of CDC20 expression inhibited the cell growth of human pancreatic carcinoma cells in vitro. Suppression of CDC20 induced accumulation of the cells in the G2/M-phase of the cell cycle. In addition, the knockdown of CDC20 caused enhancement of the cytotoxicity of paclitaxel and increased the effect of gamma-irradiation against pancreatic carcinoma cells.


CONCLUSIONS
CDC20 is a promising target for gene specific therapy in human pancreatic cancer.
Taniguchi
Koichi
K
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. t1006koichi@yahoo.co.jp
Momiyama
Nobuyoshi
N
Ueda
Michio
M
Matsuyama
Ryusei
R
Mori
Ryutaro
R
Fujii
Yoshiro
Y
Ichikawa
Yasushi
Y
Endo
Itaru
I
Togo
Shinji
S
Shimada
Hiroshi
H
D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D034741:RNA, Small Interfering; C577488:CDC20 protein, human; D017239:Paclitaxel