Gene therapy that inhibits NF-kappaB results in apoptosis of human hepatocarcinoma by recombinant adenovirus.

AIM: 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.
CONCLUSION: AdIkappaBalphaM gene therapy greatly enhances apoptosis due to inhibition of an NF-kappaB-mediated antiapoptosis signaling pathway.