The following is a summary of “Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer,” published in the March 2024 issue of Oncology by Ding et al.
Ropivacaine, a widely used local anesthetic, has demonstrated anti-tumor properties across various cancer types. However, its precise mechanisms and specific impact on breast cancer cell stemness remain poorly understood. In this study, the researchers conducted a series of in vitro and in vivo assays, including FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft model experiments, to elucidate the effects of ropivacaine on breast cancer stemness. Their results revealed a significant suppression of stem cell-like properties in breast cancer cells upon ropivacaine treatment. Subsequent RNA-seq analysis identified GGT1 as a downstream target gene responsive to ropivacaine, with high GGT1 levels correlating with poor prognosis in breast cancer.
Mechanistically, ropivacaine exerted its inhibitory effect on GGT1 expression by directly interacting with the catalytic domain of AKT1, thereby impairing its kinase activity and leading to the inactivation of NF-κB. Notably, NF-κB was found to bind to the promoter region of GGT1, establishing a positive feedback loop involving NF-κB/AKT1/GGT1/NF-κB in the regulation of ropivacaine-mediated suppression of breast cancer stemness. The findings underscore the potential clinical significance of ropivacaine in breast cancer treatment by targeting the AKT1/GGT1/NF-κB signaling pathway. These insights provide a rationale for further exploration of ropivacaine as a therapeutic agent in breast cancer management.
Source: jeccr.biomedcentral.com/articles/10.1186/s13046-024-03016-9