Oridonin regulates pituitary-derived folliculostellate cells apoptosis via the p38 MAPK/p53 signalling pathway.

Treatment of non-functioning pituitary adenoma remains challenging owing to a lack of effective pharmacological therapies. A previous study has shown that oridonin (ORI) induces apoptosis in pituitary-derived folliculostellate (PDFS) cells; therefore, this study further investigated the molecular mechanisms by which ORI-mediated regulates apoptosis in PDFS cells. To confirm the regulatory role of the p38 mitogen-activated protein kinase (MAPK)/p53 signalling pathway, molecular docking and the p38 MAPK inhibitor SB202190 were used to evaluate pathway modulation. Effects on cell viability, migration, invasion, and apoptosis were evaluated using Calcein-AM/Propidium Iodide (PI) double staining, Transwell migration and invasion assays, and Western blot analysis. To further assess the in vivo effects of ORI, a subcutaneous xenograft model in nude mice was established, and ORI was administered at 5 and 10 mg/kg to assess therapeutic efficacy and safety. Safety was evaluated by analysing histopathological changes in major organs using haematoxylin-eosin (H&E) staining. Western blot analysis of tumour tissues was conducted to assess activation of the p38 MAPK/p53 pathway and the expression of apoptosis-related proteins. Molecular docking and Western blot assays confirmed that ORI binds to p38 protein with an affinity of -7.3 kcal/mol, markedly increasing p38 phosphorylation and p53 expression. The p38 MAPK inhibitor SB202190 reversed ORI-induced effects on cell death, cell migration and invasion, and apoptosis, highlighting the critical role of the p38 MAPK/p53 pathway. ORI effectively suppressed subcutaneous tumour growth in nude mice without notable toxicity while upregulating apoptosis-related proteins Bax and cleaved caspase-3 and downregulating Bcl-2 through activation of the p38 MAPK/p53 pathway.