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Updated: May 7, 2026

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays
Published on: February 24, 2023
ATP11B mediates platinum resistance in ovarian cancer
Myrthala Moreno-Smith1, J B Halder, Paul S Meltzer
1Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
Platinum compounds display clinical activity against a wide variety of solid tumors; however, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. We found that ATP11B expression was correlated with higher tumor grade in human ovarian cancer samples and with cisplatin resistance in human ovarian cancer cell lines. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-targeted siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux kinetics indicated that ATP11B enhances the export of cisplatin from cells. The colocalization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins, such as syntaxin-6 (STX6) and vesicular-associated membrane protein 4 (VAMP4), strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, inhibition of ATP11B expression could serve as a therapeutic strategy to overcome cisplatin resistance.
Insights
Researchers discovered ATP11B, a protein linked to cisplatin resistance in ovarian cancer. Inhibiting ATP11B may help overcome this resistance, improving platinum-based chemotherapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Platinum compounds are vital in treating solid tumors.
- Cisplatin resistance, often due to altered platinum transport, limits therapeutic efficacy.
- Understanding resistance mechanisms is crucial for improving cancer treatment.
Purpose of the Study:
- To identify and characterize novel mechanisms of cisplatin resistance.
- To investigate the role of ATP11B, a P-type ATPase, in cisplatin resistance.
- To explore ATP11B as a potential therapeutic target for overcoming cisplatin resistance.
Main Methods:
- Correlation analysis of ATP11B expression with tumor grade and cisplatin resistance in human ovarian cancer.
- Assessment of cisplatin sensitivity following ATP11B gene silencing in ovarian cancer cell lines.
- In vivo efficacy studies using combined cisplatin and ATP11B-targeted siRNA therapy in mouse models.
- In vitro mechanistic studies on platinum content, efflux kinetics, and protein colocalization.
Main Results:
- ATP11B expression positively correlated with ovarian tumor grade and cisplatin resistance.
- ATP11B gene silencing resensitized resistant ovarian cancer cells to cisplatin.
- Combined therapy demonstrated significant tumor growth inhibition in vivo.
- ATP11B was found to enhance cisplatin export via vesicular transport.
Conclusions:
- ATP11B plays a significant role in mediating cisplatin resistance in ovarian cancer.
- Targeting ATP11B represents a promising strategy to enhance the effectiveness of platinum-based chemotherapy.
- Inhibition of ATP11B could overcome resistance and improve patient outcomes in solid tumors treated with cisplatin.
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