Pharmacokinetics and Pharmacological/Bioactive Studies of Oridonin Derivatives in Anti-tumor Research

Objective: it to investigate the pharmacokinetics of oridonin derivatives and their effects on tumor cell proliferation (Pro), invasion (Inv), and apoptosis (Apo), aiming to provide a theoretical basis for cancer treatment. Materials and Methods: drug and statistics (DAS) software was utilized to analyze the average blood concentration-time data collected, determining pharmacokinetic parameters. Human breast cancer MCF-7 cells were used as experimental cells. Cells were rolled into three groups: Group A (GA, 0 μM), Group B (GB, 2 μM), and Group C (GC, 4 μM) treated with 15 μL of different concentrations of oridonin derivative CYD0618. Cell Pro and cytotoxicity were evaluated using the MTT assay, while Apo, Inv, migration (Mig), and protein expression changes were assessed using flow cytometry, Transwell assays, and Western blotting, respectively. Results: over time, the average blood drug concentration gradually declined, notably within 5 hours. Pharmacokinetic analysis revealed initial distribution half-life (t1/2α) of approximately 2.104 hours, elimination half-life (t1/2β) of 69.303 hours, area under the concentration-time curve (AUC) of 41.637 mg/h/L, clearance rate (CL) of 0.089 L/h/kg, and apparent volume of distribution (V) of 0.4 L/kg. GB and GC exhibited greatly lower cell counts than GA (P<0.05), with GC showing fewer cells relative to GB (P<0.05). The Mig of tumor cells was notably reduced in GB and GC versus GA (P<0.05), and GC showed fewer migrated cells than GB (P<0.05). Furthermore, Inv of tumor cells was markedly lower in GB and GC versus GA (P<0.05), with GC demonstrating fewer invasive cells than GB (P<0.05). Apo rates were greatly higher in GB and GC relative to GA (P<0.05), and GC had a higher Apo rate than GB (P<0.05). Additionally, STAT3 and p-STAT3 levels were substantially higher in GB and GC versus GA (P<0.05), with GB showing notably higher p-STAT3 expression than GC (P<0.05). Conclusion: oridonin derivatives can inhibit tumor cell Pro, Inv, and Mig by suppressing STAT3 phosphorylation and promoting tumor cell Apo.