Combinatorial Effect of Ing4 and Trail Gene Expressing Oncolytic Adenoviruses in Hepatocellular Carcinoma Combinatorial Effect of Ing4 and Trail Gene Expressing Oncolytic Adenoviruses in Hepatocellular Carcinomaopen access
- Authors
- Oh, Eonju; Jung, Bo-Kyeong; Yun, Chae-Ok
- Issue Date
- May-2018
- Publisher
- CELL PRESS
- Citation
- MOLECULAR THERAPY, v.26, no.5, pp.332 - 332
- Indexed
- SCIE
- Journal Title
- MOLECULAR THERAPY
- Volume
- 26
- Number
- 5
- Start Page
- 332
- End Page
- 332
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/17014
- DOI
- 10.1016/j.ymthe.2018.05.001
- ISSN
- 1525-0016
- Abstract
- Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4); as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); as potent-apoptosis inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono-and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce anti-tumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.
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