Investigation of the Effect of Ruscogenin on the Passage and Metastasis of Osteosarcoma Stem Cells through the Endothelial Barrier
Project no. 32839 · Status: Kapanmış · 2025
Summary
<p>Cancer metastasis is a significant limiting factor in cancer treatments and can have fatal consequences if not diagnosed early. Despite extensive research on metastasis-suppressing genes and prognostic factors, a definitive treatment to prevent cancer metastasis has not been developed. During the metastasis process, cancer cells break free from their tumor site by overcoming physical barriers such as the endothelial barrier (EB) and spread to other tissues via blood and lymph vessels.</p><p><br></p><p>New studies suggest that a subgroup of cells called cancer stem cells (CSCs), or cancer-initiating cells, possess the ability to both self-renew and differentiate into various cancer cells. They play a decisive role in maintaining the capacity for malignant proliferation, invasion, and tumor recurrence in cancer and are also key to metastasis. Therefore, therapeutic approaches targeting CSCs are gaining increasing importance in current cancer research.</p><p><br></p><p>Ruscogenin, known to reduce cell viability and tumor growth in various cancers and to increase the expression of tight junction proteins through studies on blood-brain barrier dysfunction, was investigated for its effect on EB permeability in vitro. In this project, an in vitro EB model was created using PCL membranes and human cord blood endothelial cells (HUVEC). Different amounts of Ruscogenin were applied to the EB to assess the effect of Ruscogenin on tight junction proteins in the EB in vitro. The integrity of HUVEC cells on the PCL membrane in the in vitro EB model was monitored using transendothelial electrical resistance (TEER), and viability analyses were performed using mitochondrial activity-based cytotoxicity assay (MTT). Zonula Occulens (ZO)-1, Claudin-4, and Vimentin expression levels were visualized using immunofluorescence staining. The study results indicated that a certain dose of Ruscogenin increased the cell integrity of EB in vitro.</p>