Guangyao Mao

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.

High temperature (HT) is a common symptom of infectious myocarditis. This study investigates the effects of HT on the heat shock response (HSR) and apoptosis in cardiomyocytes, with the aim of providing insights into potential treatment strategies for myocarditis. Rat cardiomyocytes (H9c2 cells) were exposed to 42°C for 1 h, followed by a return to 37°C to simulate high fever conditions. The cells were divided into seven groups: control, oe-NC, oe-CLU, HT, HT + oe-NC, HT + oe-CLU, and HT + oe-CLU + LY294002 (PI3K inhibitor). Protein levels of HSP70, HSP90, Bax, Bcl2, CLU, p-PI3K, and p-Akt were measured by Western blot, while mRNA expression of HSP70, HSP90, Bax, Bcl2, and CLU was assessed via reverse transcription quantitative polymerase chain reaction. Cell proliferation (cell counting kit-8 assay), apoptosis (flow cytometry), and reactive oxygen species (ROS) levels (MitoSOX assay) were also evaluated. HT exposure led to decreased cell proliferation, increased apoptosis, and elevated ROS levels ( p < 0.001), while also inducing expression of HSP70 and HSP90 ( p < 0.0001). Overexpression of Clusterin (CLU) enhanced HSP70 and HSP90 levels, reduced apoptosis, improved cell proliferation, and decreased ROS under HT conditions ( p < 0.0001). The PI3K inhibitor reversed these protective effects, confirming the involvement of the PI3K/Akt pathway ( p < 0.05). CLU activates the PI3K/Akt pathway, thereby enhancing the HSR and protecting cardiomyocytes. These findings suggest that CLU could be a potential therapeutic target for myocarditis treatment.