Remimazolam impairs bone marrow mesenchymal stem cell function and attenuates the tumor-promoting ability.

Bone marrow mesenchymal stem cells (BMMSCs) possess the potential for multidirectional differentiation and are involved in tissue regeneration, repair, and tumor progression. Remimazolam is a novel ultra-short-acting intravenous benzodiazepine sedative used for general anesthesia and procedural sedation. Propofol is a commonly applied intravenous anesthetic in clinical practice, featuring a rapid onset, short duration of action, and quick recovery. It has been reported that propofol exerts adverse effects on stem cell functions, yet few studies have compared the two agents for general anesthesia induction. Therefore, we aimed not only to evaluate the inhibitory effects of remimazolam and propofol on BMMSC biological functions but also to compare their relative impacts on BMMSC proliferation, migration, stemness, and subsequent tumor-promoting capacity in vitro. CCK-8 cell viability and colony formation assays were performed to detect BMMSC proliferation. Adipogenic and osteogenic differentiation assays were used to assess the multidirectional differentiation potential of BMMSCs. Additionally, network pharmacology analysis was employed to explore the common target genes of remimazolam and propofol and their associated signaling pathways. The effects of conditioned medium from BMMSCs treated with remimazolam or propofol on gastric cancer cell lines were investigated using transwell assays, flow cytometry, and western blot. The results showed that remimazolam inhibited the proliferation and migration of BMMSCs, suppressed osteogenic differentiation, promoted adipogenic differentiation, and reduced the stemness of BMMSCs. Compared with propofol treatment, remimazolam exerted a less pronounced inhibitory effects on these biological processes of BMMSCs. Network pharmacology analysis revealed that remimazolam modulates the paracrine level of the cytokine IL-8 mainly through the PI3K/AKT pathway. Furthermore, remimazolam further attenuated the tumor-promoting effect of BMMSCs on gastric cancer cells. In conclusion, remimazolam exerts stronger inhibitory effects on the stemness and paracrine function of BMMSCs than propofol, thereby reducing their tumor-promoting capacity to a greater extent. Our study focuses on remimazolam and provides experimental evidence for the rational clinical application of anesthetics.