Cell membrane breakage and triggering T cell infiltration are involved in human telomerase reverse transcriptase (hTERT) promoter-driven novel peptide KK-64 for liver cancer gene therapy

Liver cancer is an aggressive malignancy with exhibits both high mortality and morbidity. The current treatment options are associated with several limitations, novel specific anti-cancer drugs are urgently needed to improve liver cancer treatment. In this study, a new peptide KK-64 was designed, and it showed strong cytotoxicity against liver cancer cells. To obtain the tumor targeting property, a plasmid that contains KK-64 DNA fragment and driven by human telomerase reverse transcriptase (hTERT) promoter was constructed. pcTERT-kk-64 plasmid was found to specifically inhibit the viability of liver cancer cells HepG2, induce substantial apoptosis as well as damage to the cell membranes, but had minimal effects toward normal liver HL-7702 cells. Furthermore, pcTERT-kk-64 plasmids was also noted to significantly attenuate migration and invasion of HepG2 cells. The anti-tumor effect of pcTERT-kk-64 plasmid was also observed in H22 cell-bearing mice, and it appeared to cause significant tumor regression, trigger tumor cell apoptosis, and infiltrate cytotoxicity T cells to the tumor tissues after plasmids injection. Thus, pcTERT-kk-64 plasmids showed both strong cytotoxicity and tumor selectivity in vitro and in tumor-bearing mice in liver cancer models.