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Oncolytic Adenovirus CD55-Smad4 Suppresses Cell Proliferation, Metastasis, and Tumor Stemness in Colorectal Cancer by Regulating Wnt/β-Catenin Signaling Pathway
- Source :
- Biomedicines, Vol 8, Iss 593, p 593 (2020), Biomedicines, Volume 8, Issue 12
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- During the past few decades, colorectal cancer (CRC) incidence and mortality have significantly increased, and CRC has become the leading cause of cancer-related death worldwide. Thus, exploring novel effective therapies for CRC is imperative. In this study, we investigated the effect of oncolytic adenovirus CD55-Smad4 on CRC cell growth. Cell viability assay, animal experiments, flow cytometric analysis, cell migration, and invasion assays, and Western blotting were used to detect the proliferation, apoptosis, migration, and invasion of CRC cells. The oncolytic adenovirus CD55-Smad4 was successfully constructed and effectively suppressed CRC cell proliferation in vivo and in vitro. Notably, CD55-Smad4 activated the caspase signaling pathway, inducing the apoptosis of CRC cells. Additionally, the generated oncolytic adenovirus significantly suppressed migration and invasion of CRC cells by overexpressing Smad4 and inhibiting Wnt/&beta<br />catenin/epithelial-mesenchymal transition (EMT) signaling pathway. Moreover, CRC cells treated with CD55-Smad4 formed less and smaller spheroid colonies in serum-free culture than cells in control groups, suggesting that CD55-Smad4 suppressed the stemness of CRC cells by inhibiting the Wnt/&beta<br />catenin pathway. Together, the results of this study provide valuable information for the development of a novel strategy for cancer-targeting gene-virotherapy and provide a deeper understanding of the critical significance of Smad4 in gene therapy of CRC.
- Subjects :
- Oncolytic adenovirus
Wnt/β-catenin signaling pathway
Colorectal cancer
Medicine (miscellaneous)
colorectal cancer
Biology
CD55-Smad4
General Biochemistry, Genetics and Molecular Biology
Article
medicine
Viability assay
neoplasms
lcsh:QH301-705.5
Cell growth
cell metastasis
Wnt signaling pathway
Cell migration
medicine.disease
digestive system diseases
oncolytic adenovirus
cell proliferation
tumor stemness
lcsh:Biology (General)
Apoptosis
embryonic structures
Cancer research
Signal transduction
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 8
- Issue :
- 593
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....deea91869f3cd0deb8ec432d8102f5a9