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518 Auranofin’s potential as an anticancer agent for ovarian carcinoma, unveiled through spheroidal insights and therapeutic synergy exploration
  1. Aurora Padelli,
  2. Viola Vargiu,
  3. Gretha Orlandi,
  4. Francesco La Torre,
  5. Massimiliano Fambrini and
  6. Flavia Sorbi
  1. Department of Biomedical, Experimental and Clinical Sciences, Division of Obstetrics and Gynecology, University of Florence, Florence, Italy


Introduction/Background Auranofin (AF), an FDA-approved gold compound for rheumatoid arthritis, is under consideration for drug repurposing, particularly in malignancies lacking effective targeted therapies like ovarian cancer. Ovarian cancer’s high lethality, often diagnosed late due to its silent early stages, and its unique transcoelomic metastasis via spheroids, make it a prime candidate for alternative treatments. This study aimed to assess AF’s impact on spheroid growth kinetics, regulation of protein signaling pathways, apoptosis induction, and ROS production in both immortalized three-dimensional cultures and primary ovarian carcinoma cultures. Additionally, the study explored the potential synergy between AF and Cisplatin (Cis).

Methodology 3D spheroids were generated from immortalized cancer cell lines (A2780, A2780CisR, and SKOV3) and primary ovarian carcinoma cultures obtained from 6 patients undergoing primary debulking surgeries.

Results Spheroids demonstrated elevated IC50 values for AF and Cis compared to 2D cultures, with AF consistently more effective. AF displayed dose-dependent inhibition of spheroid formation and growth, impacting signaling pathways crucial for inflammation and chemoresistance (NF-kB and pAKT) in both primary cultures and spheroids. However, the combination of AF and Cis exhibited an additive effect rather than synergy.

Conclusion The findings support Auranofin as a potential anticancer agent for ovarian cancer treatment. Future investigations should explore potential combination therapies with other drugs commonly used in ovarian cancer treatment.

Disclosures The authors have no conflicts of interest to disclose.

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