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

Abstract

AIM: To investigate whether the recombinant adenovirus induces the TNF-α-mediated apoptosis in vivo.

METHODS: Human hepatocarcinoma cell line (HepG₂) cells were transfected into BALB/c nude mice, and the tumor growth curve was drawn. We analyzed apoptosis in HepG₂ cells by TUNEL, HE staining and electron microscopy.

RESULTS: AdIκBαM was expressed stably and efficiently in HepG₂ and could not be degraded by induction of TNF-α. Tumor growth in mice could be reduced remarkably if treated by AdIκBαM plus TNF-α. There was apoptosis of > 70% of cells treated with AdIκBαM plus TNF-α and about 50% of cells treated with AdIκBαM. In contrast, there was few cell apoptosis in HepG₂ cells treated with phosphate buffered saline and AdIκBα. HepG₂ cells in mice also exhibited a high level of apoptosis after in vivo injection with AdIκBαM. The tumor growth curve indicated the tumor transfected with AdIκBαM could be restrained.

CONCLUSION: AdIκBαM gene therapy greatly enhances apoptosis due to inhibition of an NF-κB-mediated antiapoptosis signaling pathway.

Keywords: NF-κB; IκBα; Adenovirus