Objective: To study the anticancer mechanism of polyphyllin I (PPI), a Traditional Chinese Medicine, on the ovarian cancer cell line HO-8910PM in vitro.
Methods: Transwell chamber invasive assays were used to investigate the inhibitory capacity of PPI on HO-8910PM metastasis. Gene expression profiling chips was used to screen differentially expressed genes between experiment group and control group. Reverse transcription PCR and Western blotting were used to determine mRNA and protein levels.
Results: With increasing PPI concentration, the metastatic capacity of cells decreased, with significance differences between the experimental and control groups (P < 0.01) as well as between two concentration groups. Gene expression profiling identified 123 differentially expressed genes, of which 70 were downregulated and 53 were upregulated. The genes were involved in multiple signal transduction pathways, including apoptosis, proliferation and metastasis. Real-time PCR (RT-PCR) showed that differential genes PIK3C2B, Caspase 9 and Wnt5A were downregulated with increasing PPI, showing an evident dose-effect relationship. The c-Jun was an exception. As the PPI dosage increased and the exposure time was extended, c-Jun relative expression showed an upward trend. There were significant differences between the experiment and control (P < 0.05). Western blot analyses showed that PPI treatment decreased levels of Caspase 9, Wnt5A and PIK3C2B and increased activated Caspase 9, c-Jun and p-c-Jun expression levels.
Conclusion: PPI has strong antitumor and anti transfer activity. It can activate c-Jun expression and the JNK signaling pathway, elicit cell apoptosis via the mitochondrial-mediated Caspase activation pathway, and finally inhibit tumor growth and migration in vitro. The downregulation of PIK3C2B and Wnt5A jointly inhibit the proliferation and metastasis of HO-8910PM. PPI may be a novel treatment for ovarian cancer.