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Competitive Effect of Overexpressed C-Terminal of Snail-1 (Csnail) in Control of the Growth and Metastasis of Melanoma Cells Publisher Pubmed



Rostami SP1, 2 ; Dehkordi NM1, 2 ; Asgari Y1 ; Bolouri MR3, 4 ; Shayanfar N5 ; Falak R3, 4 ; Kardar GA1, 2
Authors
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Authors Affiliations
  1. 1. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Immunology Asthma & Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

Source: Recent Patents on Anti-Cancer Drug Discovery Published:2024


Abstract

Background: Epithelial-to-mesenchymal transition (EMT) plays a role in the invasion and metastasis of cancer cells. During this phenomenon, Snail can promote tumor progression by upregulating mesenchymal factors and downregulating the expression of pro-apoptotic proteins. Objective: Therefore, interventions on the expression rate of Snails may show beneficial therapeutic applications. Methods: In this study, the C-terminal region of Snail1, capable of binding to E-box genomic sequences, was subcloned into the pAAV-IRES-EGFP backbone to make complete AAV-CSnail viral particles. B16F10 as a metastatic melanoma cell line, with a null expression of wild type TP53 was transduced by AAV-CSnail. Moreover, the transduced cells were analyzed for in vitro expression of apoptosis, migration, and EMT-related genes, and in vivo inhibition of metastasis. Results: In more than 80% of the AAV-CSnail transduced cells, the CSnail gene expression competitively reduced the wild-type Snail functionality and consequently lowered the mRNA expression level of EMT-related genes. Furthermore, the transcription level of cell cycle inhibitory factor p21 and pro-apoptotic factors were promoted. The scratch test showed a decrease in the migration ability of AAV-CSnail transduced group compared to control. Finally, metastasis of cancer cells to lung tissue in the AAV-CSnail-treated B16F10 melanoma mouse model was significantly reduced, pointing out to prevention of EMT by the competitive inhibitory effect of CSnail on Snail1 and increased apoptosis of B16F10 cells. Conclusion: The capability of this successful competition in reducing the growth, invasion, and metastasis of melanoma cells indicates that gene therapy is a promising strategy for the control of the growth and metastasis of cancer cells. © 2024 Bentham Science Publishers.