Effect of protein kinase D inhibitor CRT0066101 on the cell migration of salivary adenoid cystic carcinoma
Objectives: This study aimed to investigate the impact of the protein kinase D (PKD) inhibitor CRT0066101 on the migration of salivary adenoid cystic carcinoma (SACC) cells in vitro, and to explore the underlying mechanisms in order to develop new treatment strategies for SACC.
Methods: SACC-LM cells were exposed to various concentrations of CRT0066101, and the activity of phospho-PKD was assessed using Western blotting and immunofluorescence staining. A Transwell assay was conducted to evaluate cell migration. Additionally, we analyzed the effects of CRT0066101 on proteins associated with epithelial-mesenchymal transition (EMT) through Western blotting, immunofluorescence, and quantitative real-time polymerase chain reaction (qRT-PCR). After treatment with CRT0066101, cells were treated with a proteasome inhibitor, and Snail protein levels were measured by Western blot.
Results: CRT0066101 inhibited PKD activity and significantly reduced the number of invasive SACC-LM cells. The treatment led to decreased expression of N-cadherin and Snail, while E-cadherin levels increased in these cells. The regulation of Snail protein degradation by CRT0066101 was found to be dependent on the proteasome pathway.
Conclusions: CRT0066101 effectively inhibits the migration of SACC-LM cells and modulates the expression of proteins and genes associated with EMT. This mechanism appears to be linked to the proteasome-dependent degradation of Snail.