Cathepsin B mediates HDAC inhibitor-induced epithelial-mesenchymal transition in lung cancer cells.

This study investigates the mechanisms by which histone deacetylase (HDAC) inhibitors induce epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC), focusing on the role of Cathepsin B. Lung cancer cell lines A549 and H1975 were treated with HDAC inhibitors SAHA and SB939, and various assays were conducted to assess cell viability, apoptosis, migration, invasion, and cytoskeletal changes. The expression of EMT-related proteins and Cathepsin B was analyzed using Western blotting, immunofluorescence, and quantitative PCR. The results demonstrated that HDAC inhibitors reduced cell viability and increased apoptosis while promoting EMT phenotypes, enhancing migration and invasion. Cathepsin B was identified as a key mediator of the HDAC inhibitor-induced EMT, which it promotes by interacting with and upregulating the transcription factor Slug. These findings suggest that Cathepsin B is a crucial factor in HDAC inhibitor-induced EMT in NSCLC, indicating that targeting this enzyme may provide a novel therapeutic strategy to counteract invasiveness in lung cancer.