Related Experiment Video
Updated: Mar 2, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer
Gina L Westhoff1, Yi Chen, Nelson N H Teng
1*Division of Gynecologic Oncology, Legacy Health, Portland, OR; and †Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University, Stanford, CA.
Objective:
Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo.
Methods:
Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative real-time polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets.
Results:
Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1, CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo.
Conclusion:
Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.
Insights
Aberrantly activated FOXM1 (forkhead box protein M1) drives ovarian cancer. Thiostrepton targeting FOXM1, combined with chemotherapy, demonstrated synergistic effects against chemoresistant ovarian cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- FOXM1 (forkhead box protein M1) is aberrantly activated in 84% of ovarian cancers, promoting uncontrolled cell proliferation.
- Dysregulation of the FOXM1 transcription network is a key feature of epithelial ovarian cancer.
- Thiostrepton, a thiazole antibiotic, has been shown to decrease FOXM1 expression.
Purpose of the Study:
- To investigate the potential of targeting the FOXM1 pathway with thiostrepton to enhance the efficacy of paclitaxel and cisplatin.
- To evaluate the combined effects of thiostrepton, paclitaxel, and cisplatin on human ovarian cancer ascites cells ex vivo.
- To determine if FOXM1 inhibition can overcome chemoresistance in ovarian cancer.
Main Methods:
- Human ovarian cancer cell lines and patient-derived ascites cells were treated with paclitaxel, cisplatin, and thiostrepton, individually and in combination.
- Cytotoxicity was assessed after 48 hours, and drug combination effects were quantified using the Chou and Talalay method (combination index).
- Quantitative real-time PCR was used to measure changes in FOXM1 mRNA expression and its downstream targets (e.g., CCNB1, CDC25B).
Main Results:
- Ovarian cancer cells, including patient ascites cells, exhibited overexpression of FOXM1.
- Thiostrepton treatment led to decreased FOXM1 mRNA expression and its downstream targets, inducing cell death.
- Combination therapy with thiostrepton, paclitaxel, and cisplatin demonstrated synergistic effects in chemoresistant ovarian cancer ascites cells.
Conclusions:
- Targeting FOXM1 with thiostrepton effectively reduces FOXM1 expression and induces cell death in ovarian cancer cells.
- The combination of thiostrepton with standard chemotherapeutics (paclitaxel, cisplatin) shows synergistic activity, particularly in chemoresistant cases.
- Targeting the FOXM1 pathway represents a promising novel therapeutic strategy for chemoresistant epithelial ovarian cancer.
