Exposure to HIV-protease inhibitors selects for increased expression of P-glycoprotein (ABCB1) in Kaposi's sarcoma cells

Br J Cancer. 2011 Aug 9;105(4):513-22. doi: 10.1038/bjc.2011.275.


Background: Given that HIV-protease inhibitors (HIV-PIs) are substrates/inhibitors of the multidrug transporter ABCB1, can induce ABCB1 expression, and are used in combination with doxorubicin for AIDS-Kaposi's Sarcoma (KS) treatment, the role that ABCB1 plays in mediating multidrug resistance (MDR) in a fully transformed KS cell line (SLK) was explored.

Methods: The KS cells were exposed to both acute and chronic treatments of physiological concentrations of different HIV-PIs (indinavir, nelfinavir, atazanavir, ritonavir, or lopinavir), alone or together with doxorubicin. The ABCB1 mRNA and protein expression levels were then assessed by qRT-PCR and western blotting, flow cytometry, and immunofluorescence.

Results: Chronic treatment of SLK cells with one of the five HIV-PIs alone or together resulted in increased resistance to doxorubicin. Co-treatment with one of the HIV-PIs in combination with doxorubicin resulted in a synergistic increase in resistance to doxorubicin, and the degree of resistance was found to correlate with the expression of ABCB1. The SLK cells were also revealed to be cross-resistant to the structurally unrelated drug paclitaxel.

Conclusion: These studies suggest that ABCB1 is primarily responsible for mediating MDR in SLK cells selected with either HIV-PIs alone or in combination with doxorubicin. Therefore, the roles that ABCB1 and drug cocktails play in mediating MDR in KS in vivo should be evaluated.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Antibiotics, Antineoplastic / pharmacology
  • Atazanavir Sulfate
  • Blotting, Western
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Synergism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / drug effects
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / pharmacology*
  • Humans
  • Indinavir / pharmacology
  • Lopinavir
  • Nelfinavir / pharmacology
  • Oligopeptides / pharmacology
  • Pyridines / pharmacology
  • Pyrimidinones / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ritonavir / pharmacology
  • Sarcoma, Kaposi / drug therapy*
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / virology
  • Treatment Outcome


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • Pyrimidinones
  • Lopinavir
  • Atazanavir Sulfate
  • Indinavir
  • Doxorubicin
  • Nelfinavir
  • Ritonavir