Guojie Chen

Polyphyllin H inhibits malignant progression of ovarian cancer in patient-derived xenograft mouse models by regulating CGN/RhoA/Rock2 axis: an experimental research

Background: Discovering new and effective drugs is a top priority for treating ovarian cancer, a gynecological tumor with a high mortality rate. As a major active ingredient isolated from Paris polyphylla , Polyphyllin H exhibits antitumor effect. However, its efficacy in ovarian cancer remains unknown. This study is designed to elucidate the antitumor activity and underlying mechanism of polyphyllin H in ovarian cancer. Materials and methods: Polyphyllin H was selected from 20 traditional Chinese medicine monomers based on its high anti-proliferative activity in CCK-8 assays performed on human ovarian cancer cell lines. The effects of polyphyllin H at different concentrations on cultured ovarian cancer cells were evaluated. Polyphyllin H was administered intragastrically to the cell line-derived xenograft (CDX) mice with ovarian cancer and the tumor inhibitory effects were assessed, and the potential anti-ovarian cancer mechanisms were predicted through protein sequencing. Subsequently, the therapeutic potential was further verified in patient-derived xenograft (PDX) mouse model. Results: The in vitro experiments demonstrated that polyphyllin H potently inhibited the proliferation, invasion, and migration of ovarian cancer cells while promoting cellular apoptosis. In vivo studies further confirmed that polyphyllin H significantly suppressed ovarian tumor growth, without inducing hepatic, renal and hematopoietic dysfunction, intestinal flora disturbance and major visceral histopathological change. Mechanistically, polyphyllin H upregulated cingulin (CGN) expression, blocking the RhoA/Rock2 signaling pathway to inhibit ovarian cancer malignant progression. Notably, polyphyllin H exerted promising antitumor efficacy in ovarian cancer PDX model, particularly demonstrating superior therapeutic effects against Her2-positive ovarian cancer. Conclusion: This study demonstrates that polyphyllin H inhibits the malignant progression of ovarian cancer via the CGN/RhoA/Rock2 pathway, without notable toxic and side effects. It provides a novel candidate drug for ovarian cancer therapy. Notably, the efficacy of polyphyllin H in ovarian cancer PDX models indicates its translational potential for clinical application.