[Effects of Peiminine on biological behavior and chemotherapy resistance of ovarian cancer by regulating the FOXO3-FOXM1 signaling axis].

Objective To investigate the effects of Peiminine (PMI) on the proliferation, invasion, migration, apoptosis, and chemotherapy resistance of ovarian cancer by regulating the forkhead box protein O3 (FOXO3)-forkhead box transcription factor M1 (FOXM1) signaling axis. Methods Ovarian cancer cells SKOV3 and SKOV3/cisplatin (DDP) were used as research objects. The proliferation inhibition of DDP on SKOV3 and SKOV3/DDP cells and the proliferation inhibition of of PMI on SKOV3/DDP cells were detected by MTT method. SKOV3/DDP cells were divided into control group (normal culture), DDP group (20 μg/mL DDP), L-PMI group, M-PMI group, H-PMI group (20 μg/mL DDP+50, 100, 200 μmol/L PMI), and carbenoxolone (CBX) group (20 μg/mL DDP+200 μmol/L PMI+50 ng/mL CBX). Plate cloning was applied to detect the proliferation of SKOV3/DDP cells. Transwell ^TM experiment was applied to detect the invasion and migration of SKOV3/DDP cells. Flow cytometry was applied to detect the apoptosis rate of SKOV3/DDP cells. Western blot (WB) was applied to detect the expression levels of proliferating cell nuclear antigen (PCNA), Caspase-3, multidrug resistance associated protein (MRP5), FOXO3, and FOXM1 proteins in SKOV3/DDP cells. Results Under DDP intervention, the proliferation inhibition rates of SKOV3 and SKOV3/DDP cells obviously increased in a dose-dependent manner, and the proliferation inhibition rate of SKOV3 cells was higher than that of SKOV3/DPP cells. Under PMI intervention, the proliferation inhibition rate of SKOV3/DDP cells greatly increased in a dose-dependent manner. The number of clonal cells, invasive cells, and migrating cells, the protein expressions of PCNA, MRP5 and FOXM1 in DDP group were lower than those in control group, and the apoptotic rate, the protein expressions of Caspase-3 and FOXO3 were higher than those in control group. Compared with the DDP group, the number of clonal cells, invasive cells, and migrating cells, the protein expressions of PCNA, MRP5 and FOXM1 in the L-PMI group, M-PMI group, and H-PMI group were lower, while the apoptotic rate, the protein expressions of Caspase-3 and FOXO3 were higher. The number of clonal cells, invasive cells, and migrating cells, the protein expressions of PCNA, MRP5 and FOXM1 in CBX group were higher than those in H-PMI group, and the apoptotic rate, the protein expressions of Caspase-3 and FOXO3 in CBX group were lower than those in H-PMI group. Conclusion PMI may activate FOXO3 and inhibit FOXM1, thereby suppressing the proliferation, invasion, migration, and chemotherapy resistance of ovarian cancer cells.