Research on the Inhibition of Cancer Cell Metastasis by Graphene Oxide Suppresses the Translation of the Snail mRNA

Introduction: Lung cancer is the most common malignant tumor worldwide and often presents with advanced metastasis. This study explores the effects of graphene oxide (GO) on lung cancer cell motility, investigates underlying mechanisms, and identifies potential therapeutic targets. Methods: The effects of GO on the viability and motility of lung cancer cells A549 and H226, and normal bronchial epithelial cells BEAS-2B, were assessed using cytotoxicity, scratch, and Transwell assays. Mechanisms were explored by measuring intracellular ROS, EMT-related and TGF-β pathway protein expression, cellular TGF-β release, and Snail mRNA levels, suggesting potential new targets. Results: Cytotoxicity, scratch, and Transwell experiments indicated that GO had cytotoxic effects on A549, H226, and BEAS-2B, and the effects increased with increasing GO concentration and culture time. A specific concentration of GO could significantly inhibit the cell motility of A549 and H226 within a specific time window. The results of the molecular mechanism experiment showed that within the selected GO concentration and time window, there was no significant change in intracellular reactive oxygen species (ROS); the epithelial-associated protein E-cadherin increased, the EMT regulatory protein Snail decreased, the level of TGF-β secreted by cells did not change, and the expression level of Snail mRNA increased. Conclusion: GO increases Snail mRNA but suppresses its translation, reducing EMT protein Snail and increasing E-cadherin, which further decreases tumor cell motility, offering a novel therapeutic strategy for addressing distant metastasis in lung cancer. The top section illustrates a lung with a focus on cell clusters, indicating GO inhibition of EMT, thereby leading to decreased cell migration. The lower section details the cellular process. TGF-beta binds to TGF-beta receptor on the cell membrane, initiating phosphorylation of Smad2 and Smad3 proteins. These phosphorylated Smad proteins form a complex with Smad4 and translocate into the nucleus. Inside the nucleus, the complex activates transcription of Snail DNA into Snail mRNA, which is then translated into Snail protein. Snail protein acts as a transcriptional suppressor, reducing E-cadherin expression. Graphene oxide (GO) is shown suppressing this pathway. The cytoplasm is labeled and arrows indicate the direction of processes and regulatory effects.Diagram showing TGF-beta signaling in EMT, involving Smad proteins, Snail transcription and E-cadherin suppression in cell metastasis. Keywords: graphene oxide, metastasis of lung cancer cells, epithelial-mesenchymal transition, Snail mRNA, protein synthesis