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Updated: Sep 17, 2025
Assessment of Ovarian Cancer Spheroid Attachment and Invasion of Mesothelial Cells in Real Time
Published on: May 20, 2014
Assessing Auranofin for Second-Line Use in Chemoresistant Ovarian Cancer: Effects on Tumour Spheroid and Primary Cell
Militello Rosamaria1, Becatti Matteo1, Gamberi Tania1
1Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
Abstract:
Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women and the most lethal gynaecological malignancy. The high mortality rate is primarily due to late diagnosis and the lack of targeted therapies. The gold standard treatment consists of debulking surgery followed by platinum/taxane-based chemotherapy, which is initially effective in approximately 75% of patients. However, most women experience relapse and develop chemoresistance. To date, no therapy has proven to be decisive, underscoring the need for research into second-line or alternative treatments to overcome chemoresistance and prevent relapses. Auranofin (AF) is a promising repositioned anticancer agent with a multifaceted mode of action both cancer cell type- and dose-dependent. The current study evaluated AF's cytotoxicity on multicellular tumour spheroids derived from three ovarian cancer cell lines (SKOV3, A2780, and A2780 cisplatin-resistant). Results demonstrated that AF inhibited spheroid formation and growth by inducing apoptosis. Furthermore, we showed that AF's mode of action involves the PI3K/Akt and NF-κB pathways, and we highlighted differences in drug responses between cisplatin-sensitive, resistant, and primary ovarian cancer cells. Finally, by examining the efficacy of AF and cisplatin in combination, we identified differential sensitivities among the cell lines and primary ovarian cancer cells.
Insights
Auranofin shows promise in treating ovarian cancer by inhibiting tumor growth and inducing apoptosis. This study explores its effectiveness against chemoresistant cells and its potential in combination therapies.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Ovarian cancer (OC) is a lethal gynecological malignancy with high mortality due to late diagnosis and chemoresistance.
- Current treatments like platinum/taxane chemotherapy are initially effective but often fail due to relapse and resistance.
- There is a critical need for novel therapeutic strategies to overcome chemoresistance and improve patient outcomes.
Purpose of the Study:
- To evaluate the anticancer potential of Auranofin (AF) on ovarian cancer models.
- To investigate the mechanisms of action of AF, including its effects on key signaling pathways.
- To assess the efficacy of AF in combination with cisplatin, particularly in chemoresistant ovarian cancer.
Main Methods:
- Cytotoxicity assays using multicellular tumor spheroids from sensitive and cisplatin-resistant ovarian cancer cell lines (SKOV3, A2780).
- Analysis of AF's impact on spheroid formation, growth, and induction of apoptosis.
- Investigation of AF's effects on the PI3K/Akt and NF-κB signaling pathways.
- Evaluation of combined efficacy of AF and cisplatin in various ovarian cancer cell models.
Main Results:
- Auranofin significantly inhibited ovarian cancer spheroid formation and growth.
- AF-induced cell death was mediated by apoptosis.
- AF's mechanism of action involves modulation of the PI3K/Akt and NF-κB pathways.
- Differential drug responses were observed between sensitive, resistant, and primary ovarian cancer cells.
- Combination therapy with AF and cisplatin showed varied sensitivities across cell lines.
Conclusions:
- Auranofin demonstrates significant preclinical efficacy against ovarian cancer, including chemoresistant variants.
- AF's multifaceted mechanism, involving apoptosis induction and pathway modulation, offers a promising therapeutic avenue.
- Combination strategies involving Auranofin warrant further investigation for overcoming treatment resistance in ovarian cancer.
