Dabrafenib Inhibits Egr-1-Mediated Adhesion of Thyroid Cancer Cells to Pulmonary Microvascular Endothelium.

Cell-cell adhesion between thyroid tumor cells and pulmonary endothelial cells plays a critical role in the development of lung metastases from primary thyroid cancer. Dabrafenib, a selective inhibitor for B-RAF kinase, has been approved for cancer treatment. However, its effects on pulmonary metastases originating from primary thyroid cancer remain unclear. In this study, we demonstrate that conditioned medium (CM) from the thyroid cancer SW579 cell line significantly elevated the expression of pro-inflammatory cytokines HMGB-1, IL-1β, and MCP-1 in human pulmonary microvascular endothelial cells (HPMECs), which was notably reduced by Dabrafenib. Additionally, exposure to the thyroid cancer SW579 CM increased the expression of endothelial adhesion molecules VCAM-1 and ICAM-1, as well as the adhesion of thyroid cancer SW579 cells to HPMECs, both of which were prevented by Dabrafenib. We also found that Dabrafenib mitigated oxidative stress induced by SW579 CM, as evidenced by increased glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) levels. Further investigation revealed that Dabrafenib's beneficial effects were mediated through the inhibition of Egr-1, and overexpression of Egr-1 reversed Dabrafenib's protective effect on the adhesion of thyroid cancer cells to HPMECs. Based on these results, we propose that Dabrafenib may have the potential to prevent pulmonary metastases of thyroid cancer cells.