RNA interference targeting the R2 subunit of ribonucleotide reductase inhibits growth of tumor cells in vitro and in vivo.
RNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and metastasis. Short interfering siRNA 1284 was designed to target R2. In vitro studies, in which three different human tumor cell lines (A498, HT-29 and A2058) were transfected with short interfering siRNA 1284, demonstrate sequence-specific down-regulation of R2, which coincides with a decrease in cell proliferation, and cell cycle inhibition. In vivo studies with xenograft mouse models, generated from the same tumor cell lines, indicate that treatment with short interfering siRNA 1284 leads to inhibition of tumor growth and this effect was found to be dose dependent. Taken together, these results suggest that short interfering siRNA 1284, targeting R2, has great potential to serve as a therapeutic agent towards the treatment of human cancers.
Avolio
Tina M
TM
Lorus Therapeutics Inc., Toronto, Ontario, Canada.
Lee
Yoon
Y
Feng
Ningping
N
Xiong
Keyong
K
Jin
Hongnan
H
Wang
Ming
M
Vassilakos
Aikaterini
A
Wright
Jim
J
Young
Aiping
A
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D012264:Ribonucleotide Reductases / Q000096:biosynthesis* / Q000235:genetics; D016196:S Phase / Q000187:drug effects; D014162:Transfection; D014183:Transplantation, Heterologous
D034741:RNA, Small Interfering; D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit