Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both in vitro and in an orthotopic transplanted mouse model
DC Field | Value | Language |
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dc.contributor.author | El-Shemi, Adel Galal | - |
dc.contributor.author | Ashshi, Ahmad Mohammed | - |
dc.contributor.author | Na, Youjin | - |
dc.contributor.author | Li, Yan | - |
dc.contributor.author | Basalamah, Mohammed | - |
dc.contributor.author | Al-Allaf, Faisal Ahmad | - |
dc.contributor.author | Oh, Eonju | - |
dc.contributor.author | Jung, Bo-Kyeong | - |
dc.contributor.author | Yun, Chae-Ok | - |
dc.date.accessioned | 2021-07-30T05:35:31Z | - |
dc.date.available | 2021-07-30T05:35:31Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2016-05 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/5603 | - |
dc.description.abstract | Background: Gene-based virotherapy mediated by oncolytic viruses is currently experiencing a renaissance in cancer therapy. However, relatively little attention has been given to the potentiality of dual gene virotherapy strategy as a novel therapeutic approach to mediate triplex anticancer combination effects, particularly if the two suitable genes are well chosen. Both tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interleukin-12 (IL-12) have been emerged as promising pharmacological candidates in cancer therapy; however, the combined efficacy of TRAIL and IL-12 genes for treatment of human hepatocellular carcinoma (HCC) remains to be determined. Methods: Herein, we investigated the therapeutic efficacy of concurrent therapy with two armed oncolytic adenoviruses encoding human TRAIL gene (Ad-Delta B/TRAIL) and IL-12 gene (Ad-Delta B/IL-12), respectively, on preclinical models of human HCC, and also elucidated the possible underlying mechanisms. The effects of Ad-Delta B/TRAIL+Ad-Delta B/IL-12 combination therapy were assessed both in vitro on Hep3B and HuH7 human HCC cell lines and in vivo on HCC-orthotopic model established in the livers of athymic nude mice by intrahepatic implantation of human Hep3B cells. Results: Compared to therapy with non-armed control Ad-Delta B, combined therapy with Ad-Delta B/TRAIL+Ad-Delta B/IL-12 elicited profound anti-HCC killing effects on Hep3B and HuH7 cells and on the transplanted Hep3B-orthotopic model. Efficient viral replication and TRAIL and IL-12 expression were also confirmed in HCC cells and the harvested tumor tissues treated with this combination therapy. Mechanistically, co-therapy with Ad-Delta B/TRAIL+Ad-Delta B/IL-12 exhibited an enhanced effect on apoptosis promotion, activation of caspase-3 and-8, generation of anti-tumor immune response evidenced by upregulation of interferon gamma (IFN-gamma) production and infiltration of natural killer-and antigen presenting cells, and remarkable repression of intratumor vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) expression and tumor microvessel density. Conclusions: Overall, our data showed a favorable therapeutic effect of Ad-Delta B/TRAIL+Ad-Delta B/IL-12 combination therapy against human HCC, and may therefore constitute a promising and effective therapeutic strategy for treating human HCC. However, further studies are warranted for its reliable clinical translation. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | BMC | - |
dc.title | Combined therapy with oncolytic adenoviruses encoding TRAIL and IL-12 genes markedly suppressed human hepatocellular carcinoma both in vitro and in an orthotopic transplanted mouse model | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Yun, Chae-Ok | - |
dc.identifier.doi | 10.1186/s13046-016-0353-8 | - |
dc.identifier.scopusid | 2-s2.0-84969498412 | - |
dc.identifier.wosid | 000376752300002 | - |
dc.identifier.bibliographicCitation | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, v.35 | - |
dc.relation.isPartOf | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | - |
dc.citation.title | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | - |
dc.citation.volume | 35 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | INHIBITS TUMOR-GROWTH | - |
dc.subject.keywordPlus | NK CELLS | - |
dc.subject.keywordPlus | EXPRESSING INTERLEUKIN-12 | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | VIRUS | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | COMBINATION | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | EFFICACY | - |
dc.subject.keywordAuthor | Dual gene virotherapy | - |
dc.subject.keywordAuthor | Oncolytic adenoviruses | - |
dc.subject.keywordAuthor | Interleukin-12 | - |
dc.subject.keywordAuthor | Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) | - |
dc.subject.keywordAuthor | Hepatocellular carcinoma | - |
dc.identifier.url | https://jeccr.biomedcentral.com/articles/10.1186/s13046-016-0353-8 | - |
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