Zengmian Yiliu formula suppresses cell cycle in immune-rich ovarian cancer patient-derived organoids
Ovarian cancer, often diagnosed at advanced stages, has a 5-year survival rate below 50%, indicating a critical need for innovative treatments. The Zengmian Yiliu (ZMYL) formula, a Traditional Chinese Medicine (TCM) prescription, has shown potential in enhancing chemotherapy efficacy and improving patients' quality of life, PURPOSE: To investigate the effects of the ZMYL formula on ovarian cancer organoids, focusing on its impact on organoid phenotypes and underlying mechanisms, and to explore its potential as an immunotherapeutic agent. Ovarian cancer organoids were established from surgical tissues and treated with the ZMYL formula at varying concentrations. Network pharmacology was utilized to predict the formula's therapeutic targets and pathways, and molecular docking was conducted to validate ingredient-target interactions. Phenotypic changes were monitored, and RNA sequencing was performed post-treatment to analyze gene expression alterations. A total of 34 overlapping targets of 10 compounds in the ZMYL formula and ovarian cancer were predicted by Network pharmacology analysis. The ZMYL formula induced dose-dependent morphological changes in organoids, including a reduction in size and structural sparsity at higher concentrations. RNA sequencing revealed significant modulation of cell cycle and immune response pathways, with a particular focus on immunomodulatory effects. The formula's treatment targeted key genes involved in these processes, reshaping the tumor's molecular landscape. This study establishes ZMYL's capacity to simultaneously target oncogenic drivers (e.g., cell cycle regulators) and immune checkpoints (e.g., CXCL10-mediated T cell recruitment) in ovarian cancer organoids. Unlike conventional monotherapy-focused approaches, ZMYL's multi-component mechanism offers a synergistic framework for integrating TCM with modern immunotherapies. These findings provide a foundation for future clinical evaluation of ZMYL as a precision medicine strategy to enhance treatment efficacy and mitigate chemoresistance in ovarian cancer.