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A comparative proteomic study to characterize the vinblastine resistance in human ovarian cancer cells
Dawn P G Brown1, Yesim Gökmen-Polar, Li Jiang
1Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Abstract:
Drug resistance is a major impediment to the successful treatment of human cancers, including ovarian cancer. Vinblastine (VLB), an antimicrotubule agent, is one of the chemotherapeutic drugs that exhibit resistance in ovarian cancer patients. To determine the protein factors that are involved in vinblastine resistance in human ovarian cancer cells, a combination of sample pre-fractionation and high-resolution 2-DE proteomic analysis was performed. Approximately 1200 proteins were detected and quantitatively compared in both nuclear/membrane and cytosolic fractions. Sixty-nine proteins from the nuclear/membrane fraction showed altered expression levels, whereas 59 were altered in the cytosolic fraction between SKOV3 (vinblastine-sensitive) and SKVLB (vinblastine-resistant) cell lines. These proteins include membrane-associated, chromatin remodeling, cytoskeletal, and microtubule-associated proteins as well as others that regulate signal transduction. This study not only demonstrates a novel understanding of the mechanism of drug resistance but also provides a valuable resource for future studies on drug resistance to vinblastine. In addition, it also represents a good example of how to increase the protein dynamic range and reduce sample complexity using currently available tools.
Insights
Drug resistance in ovarian cancer is a major challenge. This study identifies key proteins involved in vinblastine resistance using advanced proteomic analysis, offering new insights into treatment strategies.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Drug resistance, particularly to chemotherapeutic agents like vinblastine (VLB), significantly hinders ovarian cancer treatment.
- Understanding the molecular mechanisms of VLB resistance is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To identify and characterize protein factors contributing to vinblastine resistance in human ovarian cancer cells.
- To provide a comprehensive proteomic profile of drug-resistant versus drug-sensitive ovarian cancer cell lines.
Main Methods:
- Utilized high-resolution 2-DE proteomic analysis combined with sample pre-fractionation.
- Quantitatively compared protein expression in nuclear/membrane and cytosolic fractions of sensitive (SKOV3) and resistant (SKVLB) ovarian cancer cell lines.
- Detected and analyzed approximately 1200 proteins.
Main Results:
- Identified 69 differentially expressed proteins in the nuclear/membrane fraction and 59 in the cytosolic fraction between sensitive and resistant cell lines.
- Altered proteins include those involved in membrane association, chromatin remodeling, cytoskeleton, microtubule function, and signal transduction.
- Demonstrated altered expression of proteins critical for cellular processes affected by vinblastine.
Conclusions:
- The study reveals novel protein factors contributing to vinblastine resistance in ovarian cancer.
- Findings offer a valuable resource for future research into overcoming vinblastine resistance.
- Highlights the utility of advanced proteomic techniques for dissecting complex biological problems like drug resistance.
