Gene transfer of inhibitor kappaB in human lung cancer cell line NCI-H460 inhibits tumorigenesis and angiogenesis in vivo.
BACKGROUND
Nuclear factor kappaB (NFkappaB) is an inducible and ubiquitously expressed transcription factor which is involved in cell survival, differentiation and growth and, thus, has also been implicated in tumor formation and development. Research on the effect of NFkappaB in inhibiting cancer cell growth, however, remains controversial.


METHODS
We investigated the effects of overexpressed IkappaBalpha on the proliferation of the human lung cancer cell line H460 in vitro and in vivo using IkappaBalpha-expressing adenovirus.


RESULTS
The results suggested that the infection of AdIkappaBalpha blocked NFkappaB activity in H460 cells and significantly inhibited cell proliferation by inducing apoptosis. An in vivo study showed the tumor incidence to be significantly lower in mice implanted with H460 cells infected with AdIkappaBa. For established H460 tumor, the intratumoral injection of AdIkappaBalpha also inhibited the tumor growth due to both a blockade of the NFkappaB activity and an inhibition of the VEGF expression.


CONCLUSIONS
Adenovirus-mediated IkappaBalpha gene transfer is a promising cancer treatment strategy.
Ni
Jian
J
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
Takayama
Koichi
K
Inoshima
Naoko
N
Uchino
Junji
J
Harada
Akiko
A
Minami
Takahiro
T
Harada
Taishi
T
Zhou
Caicun
C
Nakanishi
Yoichi
Y
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology / Q000628:therapy; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D042461:Vascular Endothelial Growth Factor A; D000072000:NF-KappaB Inhibitor alpha; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases