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Updated: Sep 21, 2026
Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
[Experimental study on the mechanism of cisplatin resistance and its reversion in human ovarian cancer]
Objective:
To explore the mechanism of cisplatin resistance and its reversion in human ovarian cancer.
Methods:
A xenografted cisplatin resistant mice model of human ovarian cancer, SKOV3/cp, was developed by the microencapsulated technique. The multiple changes of bio-chemical markers in the model were determined, and various modulators for reversion were tested.
Results:
Intracellular platinum accumulation in SKOV3 was 5.1 times, Pt-DNA adducts 2.4 times and interstrand cross link of DNA (ISC) 4.8 times of those in cisplatin-resistant cell line, SKOV3/cp. These changes in SKOV3/cp could not be reversed by verapamil. Amphotercin B (AmB) and Novobiocin (NVB) could raise the concentrations of platinum and Pt-DNA adducts in SKOV3/cp, resulting in complete or partial reversion of cisplatin-resistance of SKOV3/cp. There were no differences in total glutathione (GSH) level and in sensitivity to CdCl2 between SKOV3 and SKOV3/cp.
Conclusions:
It is suggested that the primary factor causing SKOV3/cp resistance to cisplatin is the reduction of intracellular platinum accumulation and the augmentation of the ability to remove Pt-DNA adducts. The resistance is not considered to be associated with the multidrug resistant, GSH, metallothionein systems. AmB and NVB can overcome cisplatin resistance of SKOV3/cp in vitro and in vivo.
Insights
Cisplatin resistance in ovarian cancer is linked to lower platinum levels and faster DNA repair. Amphotericin B and Novobiocin can reverse this resistance by increasing platinum accumulation and DNA adducts.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Cisplatin is a cornerstone chemotherapy for ovarian cancer.
- Acquired cisplatin resistance remains a significant clinical challenge.
- Understanding resistance mechanisms is crucial for developing effective treatment strategies.
Purpose:
- To investigate the mechanisms underlying cisplatin resistance in human ovarian cancer.
- To explore methods for reversing cisplatin resistance.
- To identify potential therapeutic targets for overcoming drug resistance.
Summary:
- A cisplatin-resistant ovarian cancer model (SKOV3/cp) was developed using microencapsulation.
- Reduced intracellular platinum accumulation and enhanced DNA repair were identified as key resistance factors.
- Amphotericin B (AmB) and Novobiocin (NVB) demonstrated efficacy in reversing cisplatin resistance in vitro and in vivo.
Impact:
- This study elucidates novel mechanisms of cisplatin resistance in ovarian cancer.
- Identifies AmB and NVB as potential agents to overcome chemoresistance.
- Provides a foundation for developing combination therapies to improve patient outcomes.
