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Updated: Feb 28, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Platinum-containing compound platinum pyrithione suppresses ovarian tumor proliferation through proteasome inhibition
Hongbiao Huang1,2, Ni Liu1,2, Yuning Liao2
1Key Laboratory of Protein Modification and Degradation, Department of Obsterics and Gynecology, The Third Affiliated Hospital, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou, Guangdong, 510510, China.
Background:
Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent.
Method:
MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis. Protein signaling pathways were detected by western blot and immunohistochemical staining. Nude mouse experiment was performed to test the in vivo effect of platinum pyrithione (PtPT).
Results:
PtPT is a chemically well-characterized synthetic complex of platinum that potently inhibits proteasome-associated deubiquitinases USP14 and UCHL5 activity and shows selective cytotoxicity to multiple cancer cells without damaging DNA. We found that PtPT significantly accumulated ubquitinated-proteins and suppressed the proliferation of multiple EOC cells. Additionally, PtPT induced G2 phase arrest and apoptosis in both A2780 and SKOV3 cells. More importantly, animal experiments showed that PtPT dramatically suppressed the growth of EOC xenografts without obvious side effects.
Conclusion:
These results suggest that through proteasome inhibition, PtPT significantly suppressed the proliferation of EOC in vitro and in vivo and could be developed as a novel agent for EOC treatment in the future.
Insights
Platinum pyrithione (PtPT) effectively inhibits proteasome activity, suppressing epithelial ovarian cancer (EOC) cell proliferation and tumor growth in vivo. This novel agent shows promise for treating EOC, overcoming chemotherapy resistance.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Ovarian carcinoma is an aggressive gynecological malignancy, with chemotherapy resistance posing a significant challenge.
- Novel therapeutic agents are urgently needed for Epithelial Ovarian Cancer (EOC) treatment.
Purpose of the Study:
- To investigate the efficacy of platinum pyrithione (PtPT) as a novel therapeutic agent for Epithelial Ovarian Cancer (EOC).
Main Methods:
- Cell viability and proliferation assessed by MTS assay.
- Cell cycle and apoptosis analyzed via flow cytometry.
- In vivo efficacy evaluated using nude mouse xenograft models.
Main Results:
- PtPT inhibited proteasome-associated deubiquitinases USP14 and UCHL5, accumulating ubiquitinated proteins.
- PtPT suppressed EOC cell proliferation, induced G2 phase arrest, and promoted apoptosis in vitro.
- PtPT significantly inhibited EOC xenograft growth in vivo with minimal side effects.
Conclusions:
- PtPT demonstrates potent anti-cancer activity against EOC through proteasome inhibition.
- PtPT shows potential as a novel therapeutic agent for EOC treatment.
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