Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion
| Autor: | Yan-Qun Liu, Guan Jiang, Yang Cs, Tiechi Lei, Chao Sun, Junnian Zheng, Xu D |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Gene Expression Regulation
Viral Male Cancer Research Cell division conditionally replicating adenoviruses Recombinant Fusion Proteins Mice Nude Apoptosis Biology medicine.disease_cause Virus Replication Adenovirus E1B protein Defective virus Adenoviridae Mice Cell Movement Cell Line Tumor medicine melanoma Genes Synthetic Animals Humans Neoplasm Invasiveness Adenovirus E1B Proteins Promoter Regions Genetic Molecular Diagnostics Oncolytic Virotherapy Mice Inbred BALB C Melanoma Interleukins Defective Viruses interleukin-24 medicine.disease Molecular biology Xenograft Model Antitumor Assays Oncolytic virus Ki-67 Antigen Oncology Viral replication Ki67 promoter Cancer research cancer therapy Cell Division |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells. Methods: Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT–PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay. Results: Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice. Conclusions: This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma. |
| Databáze: | OpenAIRE |
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