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



Rostami SP^{1, 2} ; Dehkordi NM^{1, 2} ; Asgari Y¹ ; Bolouri MR^{3, 4} ; Shayanfar N⁵ ; Falak R^{3, 4} ; Kardar GA^{1, 2} Show Affiliations
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.