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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Research Article

Competitive Effect of Overexpressed C-terminal of Snail-1 (CSnail) in Control of the Growth and Metastasis of Melanoma Cells

Author(s): Sadegh Paydari Rostami, Negar Moghare Dehkordi, Yazdan Asgari, Mohammad Reza Bolouri, Nasrin Shayanfar, Reza Falak and Gholam Ali Kardar*

Volume 19, Issue 3, 2024

Published on: 03 May, 2023

Page: [342 - 353] Pages: 12

DOI: 10.2174/1574892818666230330105016

Price: $65

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.

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