Gene therapy that inhibits NF-kappaB results in apoptosis of human hepatocarcinoma by recombinant adenovirus.
OBJECTIVE
To investigate whether the recombinant adenovirus induces the TNF-alpha-mediated apoptosis in vivo.


METHODS
Human hepatocarcinoma cell line (HepG(2)) cells were transfected into BALB/c nude mice, and the tumor growth curve was drawn. We analyzed apoptosis in HepG(2) cells by TUNEL, HE staining and electron microscopy.


RESULTS
AdIkappaBalphaM was expressed stably and efficiently in HepG(2) and could not be degraded by induction of TNF-alpha. Tumor growth in mice could be reduced remarkably if treated by AdIkappaBalphaM plus TNF-alpha. There was apoptosis of > 70% of cells treated with AdIkappaBalphaM plus TNF-alpha and about 50% of cells treated with AdIkappaBalphaM. In contrast, there was few cell apoptosis in HepG(2) cells treated with phosphate buffered saline and AdIkappaBalpha. HepG(2) cells in mice also exhibited a high level of apoptosis after in vivo injection with AdIkappaBalphaM. The tumor growth curve indicated the tumor transfected with AdIkappaBalphaM could be restrained.


CONCLUSIONS
AdIkappaBalphaM gene therapy greatly enhances apoptosis due to inhibition of an NF-kappaB-mediated antiapoptosis signaling pathway.
Li
Tie-Jun
TJ
Center of Blood Purification, The 9th Hospital of Chongqing, Beibei 400700, Chongqing, China.
Jia
Li-Ping
LP
Gao
Xiao-Ling
XL
Huang
Ai-Long
AL
D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000628:therapy*; D002460:Cell Line; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008854:Microscopy, Electron; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha