For the first time, it was shown the possibility to induce the exogenous expression of the pro-apoptotic gene TRAIL and p53 in a liver cancer HepG2 cells via a sonoporation procedure.
Since the cancer stem cells (CSCs) are believed to be responsible for the treatment failure in multiple cancers including hepatocellular carcinoma (HCC), the aim of this study was to investigate the strategies to increase the sensitivity of liver cancer stem cells (LCSCs) to TRAIL.
To establish the combined anti-tumor therapeutic effect of endostatin and soluble TRAIL (sTRAIL), we performed intra-tumoral human endostatin and sTRAIL gene transfer using plasmid pVAX1 as a vector in a nude mouse model of human liver cancer.
Our results reveal a new AP-1 site within the TRAIL promoter functionally involved in TGF-beta-induced TRAIL expression and apoptosis in hepatomas and thus provide evidence for the underlying mechanism by which TGF-beta might regulate cell death in liver cancer.
We demonstrated that our oncolytic vector (Ad5/35.IR-E1A/TRAIL) induced apoptosis in human tumor cell lines derived from colorectal, lung, prostate, and liver cancer.