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Updated: Feb 27, 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 reverse transcriptase-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 and 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
Targeting FOXM1 with thiostrepton reduced ovarian cancer cell proliferation and enhanced chemotherapy efficacy. This approach shows promise for treating chemoresistant epithelial ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Aberrant activation of FOXM1 (forkhead box protein M1) drives uncontrolled cell proliferation in 84% of ovarian cancer cases.
- FOXM1 dysregulation is a key factor in ovarian cancer progression and chemoresistance.
- Thiostrepton, a thiazole antibiotic, has been shown to decrease FOXM1 expression.
Purpose of the Study:
- To investigate the efficacy of targeting the FOXM1 pathway with thiostrepton in human ovarian cancer ascites cells.
- To determine if combining thiostrepton with paclitaxel and cisplatin improves treatment outcomes in ovarian cancer.
- To assess the impact of FOXM1 inhibition on chemoresistant ovarian cancer cells ex vivo.
Main Methods:
- Human ovarian cancer cell lines and patient ascites cells were treated with paclitaxel, cisplatin, and thiostrepton, alone or in combination.
- Cytotoxicity was evaluated after 48 hours of treatment.
- FOXM1 expression and its downstream targets (e.g., CCNB1, CDC25B) were analyzed using quantitative reverse transcriptase-polymerase chain reaction.
Main Results:
- Overexpression of FOXM1 was confirmed in ovarian cancer cell lines and patient ascites cells.
- Thiostrepton treatment significantly 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 ovarian cancer cell viability and proliferation.
- The combination of thiostrepton with standard chemotherapeutics offers a potential strategy to overcome chemoresistance in epithelial ovarian cancer.
- Inhibition of the FOXM1 pathway represents a promising therapeutic avenue for developing novel treatments for chemoresistant ovarian cancer.
