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

摘要

AIM: To investigate whether the recombinant adenovirus induces the TNF-α-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: AdIκBαM was expressed stably and efficiently in HepG_2 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 HepG_2 cells treated with phosphate buffered saline and AdIκBα. HepG_2 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.