Exposure to HIV-protease inhibitors selects for increased expression of P-glycoprotein (ABCB1) in Kaposi's sarcoma cells
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
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| Enthalten in: |
British journal of cancer - 105(2011), 4 vom: 09. Aug., Seite 513-22 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lucia, M B [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.09.2011 Date Revised 10.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1038/bjc.2011.275 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM210632542 |
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| 100 | 1 | |a Lucia, M B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exposure to HIV-protease inhibitors selects for increased expression of P-glycoprotein (ABCB1) in Kaposi's sarcoma cells |
| 264 | 1 | |c 2011 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.09.2011 | ||
| 500 | |a Date Revised 10.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 7 | |a ABCB1 protein, human |2 NLM | |
| 650 | 7 | |a ATP Binding Cassette Transporter, Subfamily B |2 NLM | |
| 650 | 7 | |a ATP Binding Cassette Transporter, Subfamily B, Member 1 |2 NLM | |
| 650 | 7 | |a Antibiotics, Antineoplastic |2 NLM | |
| 650 | 7 | |a HIV Protease Inhibitors |2 NLM | |
| 650 | 7 | |a Oligopeptides |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
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| 700 | 1 | |a Anu, R |e verfasserin |4 aut | |
| 700 | 1 | |a Handley, M |e verfasserin |4 aut | |
| 700 | 1 | |a Gillet, J-P |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, C-P |e verfasserin |4 aut | |
| 700 | 1 | |a De Donatis, G M |e verfasserin |4 aut | |
| 700 | 1 | |a Cauda, R |e verfasserin |4 aut | |
| 700 | 1 | |a Gottesman, M M |e verfasserin |4 aut | |
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