Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference.
Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.
Sumimoto
H
H
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Yamagata
S
S
Shimizu
A
A
Miyoshi
H
H
Mizuguchi
H
H
Hayakawa
T
T
Miyagishi
M
M
Taira
K
K
Kawakami
Y
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018288:Carcinoma, Small Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006678:HIV / Q000235:genetics; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D034622:RNA Interference; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics*
D044786:S-Phase Kinase-Associated Proteins