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

Zhang,Haitao; Qin,Ling; Li,Chaolu; Jiang,Jianyi; Sun,Libo; Zhao,Xiaofei; Li,Ning

doi:10.3892/etm.2019.7147

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

Authors:
- Haitao Zhang
- Ling Qin
- Chaolu Li
- Jianyi Jiang
- Libo Sun
- Xiaofei Zhao
- Ning Li
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Affiliations: Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China, Department of Biomedical Information Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China, Department of Surgery, Shijingshan Hospital of Beijing, Beijing 100040, P.R. China
Published online on: January 2, 2019 https://doi.org/10.3892/etm.2019.7147
Pages: 1649-1655
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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