Adenovirus‑mediated herpes simplex virus thymidine kinase gene therapy combined with ganciclovir induces hepatoma cell apoptosis

Abstract

The present study aimed to examine the apoptotic effects of adenovirus (ADV)-mediated herpes simplex virus thymidine kinase (ADV-TK) combined with ganciclovir (GCV) in tissues obtained from patients with hepatocellular carcinoma in order to provide a theoretical basis for the development of this gene therapy program. Apoptosis detection was conducted using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling assay and the apoptosis index was compared between the experimental; and control groups. Furthermore, the protein expression levels of caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-assoicated protein X (Bax) and nuclear factor (NF)-κB were examined in pathological specimens using immunohistochemical staining. The Bax/Bcl-2 ratio and the release of cytochrome c were examined using western blot analysis. Results indicated that combined ADV-TK and GCV treatment significantly increased the number of apoptotic cells compared with the control group (P<0.05). Immunohistological analysis revealed that ADV-TK and GCV treatment significantly increased the number of caspase-3-positive cells, reduced the Bax/Bcl-2 ratio and NF-κB expression levels and promoted the release of cytochrome c compared with the control group (P<0.01). In conclusion, the present results suggest that combined ADV-TK and GCV treatment exerts its effect through the apoptotic signaling pathway.