An In Vitro and In Vivo Investigation of the Antimetastatic Effects of a Chinese Medicinal Decoction, Erxian Decoction, on Human Ovarian Cancer Models

摘要

Objectives. Erxian Decoction (EXD) is a well-documented Chinese medicinal formulation, which has been clinically applied for years for relieving menopausal syndromes by modulating hormonal levels indicating that EXD might also be effective in treating hormone-related tumors. This study aimed to differentially investigate the efficacy of EXD and its antimetastatic property on human ovarian cancer cells, OVCA429. Methods. The efficacy and cell cycle progression of EXD on OVCA429 cells was determined by MTT assay and flow cytometry, respectively. The modulated expression of metastatic markers by EXD in OVCA429 cells and xenografts was evaluated at transcriptional and translational levels by Western blotting and real-time polymerase chain reaction, respectively. The migrating and invasive ability of the cancer cells were determined by wound healing and invasive assays. Results. The IC₅₀ value of EXD on OVCA429 cells was determined after 24 hours incubation with EXD at 1 mg/mL. EXD (1.5 mg/mL) mediated S-phase cell cycle arrest and apoptotic cell death at 24 hours posttreatment. EXD repressed the expression of several metastatic mediators, including EGFR, ErbB2, MMP2, MMP7, MMP9, and VEGF in OVCA429 cells and xenografts at transcriptional and/or translational levels. Furthermore, EXD functionally demonstrated significant inhibition of migrating and invasive ability of OVCA429 cells. EXD suppressed tumor size in xenografts without any adverse effects on body weight. Conclusions. This is the first study that illustrates the antimetastatic property of EXD on human ovarian cancer models. This decoction merits serious consideration for further delineation of its multiple pharmacological effects, especially on hormone-related cancers, and these would be valuable for future clinical applications of EXD as an alternative regime for cancers.