Abstract: Objective To study the inhibitory effect of Guizhi Fuling Capsule (GFC) on migration of human ovarian cancer cells and explore the possible mechanism. Methods Sixty Wistar rats were randomized into 4 groups for daily gavage of saline or 4, 8, or 16 g/kg GFC suspension for 5 days to prepare blank and low-, medium- and high-dose GFC-medicated sera. Cisplatin-resistant ovarian cancer SKOV3/DDP cells were treated with these sera with nuclear factor-κB (NF-κB) inhibitor SN50 as the positive control, and the changes in migration ability and apoptosis of the cells were examined using scratch assay and flow cytometry, respectively; the changes in the mRNA and protein expressions of CDH1, CDH2, caspase 3 and NF- κB were detected using RT- qPCR and Western blotting. ATAC- seq was used to analyze the changes in expressions of CDH1, CDH2, caspase 3 and NF-κB genes in the open chromatin. Results Treatment with GFC-medicated sera dose-dependently inhibited the migration (P<0.05), increased apoptosis (P<0.01), inhibited CDH2 and NF-κB mRNA expression (P<0.05), and enhanced caspase 3 and CDH1 mRNA expressions (P<0.01) in SKOV3/DDP cells. The effects of high-dose GFC-medicated serum were comparable to those of SN50 (P>0.05), but its effect for enhancing DH1 protein expression was weaker than that of SN50 (P<0.01). GFC-medicated sera significantly lowered the expressions of NF-κB and CDH2 and increased CDH1 expression in the open chromatin without obviously affecting caspase 3 expression. Conclusion GFC- medicated sera inhibits the migration ability of SKOV3/DDP cells possibly by promoting cell apoptosis and caspase 3 and CDH1 expressions, inhibiting CDH2 and NF-κB expressions, and regulating the expressions of NF-κB, CDH2 and CDH1 in the open chromatin.

Key words: ovarian cancer; Guizhi Fuling Capsule; nuclear factor- kappa B; E-cadherin; N-cadherin; epithelial-mesenchymal transition; caspase 3