Therapeutic effects of ephrin B receptor 2 inhibitors screened by molecular docking on cutaneous squamous cell carcinoma

Background: Cutaneous squamous cell carcinoma (CSCC) is the most known form type of metastatic skin cancer. Activation of ephrin B receptor 2 (EphB2) signaling can promote the metastasis, invasion, and angiogenesis of CSCC cells. Therefore, EphB2 may act as a therapeutic target for CSCC. Here, we screened the inhibitors for EphB2 using molecular docking and then evaluated the effects of the identified inhibitors on cancer-related features of CSCC cells. Methods: The Schrodinger docking tool was used to predict the three-dimensional structure of EphB2 protein and its ligand binding sites, and EphB2 inhibitors were screened by high-throughput virtual screening combined with molecular docking. The effects of EphB2 inhibitors were analyzed for cell viability, proliferation, apoptosis, migration, invasion, and xenograft tumor growth. Results: In vitro experiments, the identified small-molecule inhibitors markedly inhibited the skin cancer cells proliferation, induced apoptosis, altered the cell cycle, and inhibited cell invasion and migration in our study. In a xenograft model, the identified small-molecule inhibitors induced changes in the epithelial mesenchymal transition, which affected the progression of CSCC. Conclusion: EphB2 small-molecule inhibitors had anti-CSCC effects, establishing a solid theoretical basis for clinical research.

Automated summary

In this study, inhibitors of EphB2 were screened using molecular docking and their effects on CSCC cells were evaluated. The identified inhibitors significantly inhibited skin cancer cell proliferation, induced apoptosis, and inhibited cell invasion and migration. In vivo, the inhibitors also affected the progression of CSCC.