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Detection of Expressed Recombinant Protein Based on Multidrug Resistance: P-Glycoprotein

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Recombinant Protein Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 63))

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Abstract

The simultaneous resistance of cells to multiple structurally and functionally unrelated cytotoxic agents is known as multidrug resistance (MDR). The phenomenon of MDR was first observed in the clinic in tumors of patients undergoing chemotherapy. Multidrug resistance was recognized as a major factor contributing to the failure of chemotherapeutic treatment of cancer (1). Multidrug resistance also occurs in cultured cells selected for resistance to anticancer drugs (2,3). Exposure of cultured cells to a single cytotoxic agent, e.g., Adriamycin (or doxorubicin) will enhance their resistance to anthracyclins and related agents (daunorubicin, idarubicin, mitoxantrone), as well as to Vinca alkaloids (e.g., vincristine, vinblastine), epipodophyllotoxins (VP-16 [etoposide] and VM-26 [teniposide]), and other anticancer drugs (e.g., actinomycin D, mitomycin C, and topotecan) (4,5). Numerous cell lines have been established as in vitro model systems to demonstrate the clinical relevance of MDR, to elucidate its molecular basis and mechanism(s), and to design therapeutically applicable strategies to circumvent and overcome MDR (6). Frequently, MDR is due to reduced intracellular accumulation of drugs resulting from overexpression of the MDR (mdr) gene product P-glycoprotein (pgp), also known as the multidrug transporter. P-glycoprotein is thought to act as an energy-dependent drug efflux pump at the cell surface (4,5). Increased levels of P-glycoprotein correlate with increased MDR. Efforts directed at circumventing or overcoming MDR in the clinic are focused on inhibition or modulation of P-glycoprotein function or MDR1 gene expression. Approaches include rational design and screening for P-glycoprotein inhibitory compounds (so-called MDR modulators, MDR reversing agents, or chemosensitizers), inhibitory antibodies, or antisense oligodeoxynucleotides (7).

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Authors and Affiliations

    Authors
    1. Ursula A. Germann
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    Editors and Affiliations

    1. Thomas Jefferson University, Philadelphia, PA

      Rocky S. Tuan

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    © 1997 Humana Press Inc., Totowa, NJ

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    Germann, U.A. (1997). Detection of Expressed Recombinant Protein Based on Multidrug Resistance: P-Glycoprotein. In: Tuan, R.S. (eds) Recombinant Protein Protocols. Methods in Molecular Biology™, vol 63. Humana Press. https://doi.org/10.1385/0-89603-481-X:139

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    • DOI: https://doi.org/10.1385/0-89603-481-X:139

    • Publisher Name: Humana Press

    • Print ISBN: 978-0-89603-481-5

    • Online ISBN: 978-1-59259-549-5

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