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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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An Orthotopic Murine Model of Human Prostate Cancer Metastasis

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Flow Cytometric Analysis of Nucleoside Transporters Activity in Chemoresistant Prostate Cancer Model

S Drápela, R Fedr, P Khirsariya

    Klinicka Onkologie : Casopis Ceske a Slovenske Onkologicke Spolecnosti
    |May 30, 2018
    PubMed
    Abstract

    Insights

    Drug resistance in cancer limits nucleoside analogue effectiveness. This study shows fluorescent probes can detect nucleoside transporter activity, linking it to drug sensitivity in prostate cancer cells.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Pharmacology

    Background:

    • Nucleoside analogues are vital antimetabolites for cancer therapy, but drug resistance diminishes their efficacy.
    • Tumor cell nucleoside transport, mediated by SLC28 (hCNTs) and SLC29 (hENTs) families, is crucial for antimetabolite uptake and treatment success.
    • Reduced nucleoside transporter function is linked to treatment failure in various cancers, including pancreatic adenocarcinoma and prostate cancer.

    Purpose of the Study:

    • To investigate the role of nucleoside transporters in chemoresistance.
    • To evaluate the utility of fluorescent nucleoside analogues for assessing transporter activity.
    • To establish a link between nucleoside transporter expression/activity and sensitivity to nucleoside analogues in prostate cancer.

    Main Methods:

    • Utilized flow cytometry with the fluorescent nucleoside analogue uridine-furane to analyze nucleoside transporter activity.
    • Employed docetaxel-resistant PC3 prostate cancer cells and their parental line for comparative analysis.
    • Combined flow cytometry, confocal microscopy, and qRT-PCR to quantify transporter activity and mRNA expression.

    Main Results:

    • Quantified the long-term kinetics of uridine-furane incorporation in PC3 cells and their resistant derivatives.
    • Demonstrated an association between nucleoside transporter activity and mRNA expression levels.
    • Showed a correlation between transporter status and sensitivity to various nucleoside analogues.

    Conclusions:

    • Fluorescent techniques offer an effective method for detecting nucleoside transporter activity.
    • Nucleoside transporter activity is a potential biomarker for predicting response to nucleoside analogue chemotherapy.
    • This approach holds promise for clinical oncology applications in managing drug resistance.

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