Abstract | OBJECTIVE: To explore the efficacy of PSC 833 on multidrug resistance (MDR) reversal and its mechanism. METHODS: Human erythroleukemic cell line K562 and its doxorubicin-resistant counterpart K562/A02 were used in the study. Cytotoxicity was assessed by MTT assay, P-gp expression by direct immunofluorescence and mdr1 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR) with beta-actin as internal control. Intracellular DNR retention was measured with flow cytometry. RESULTS: K562/A02 cells displayed high levels of mdr1 mRNA and P-glycoprotein and reduced DNR retention compared to their parental K562 cells. 1 micromol/L of PSC 833 had no effect on the levels of mdr1 mRNA and P-gp expression in K562/A02 cells (P > 0.05). PSC 833 conferred a dose-dependent increase on chemosensitivity of K562/A02 to DNR, and its effect was at least 3-fold more potent than that of CsA or Ver. PSC 833 could increase DNR retention in K562/A02 cells. A 100.9% restoration of intracellular DNR retention of the level of K562 cells was gained by PSC 833 at 1.0 micromol/L in K562/A02 cells, whereas only a 86.9% restoration of DNR retention was obtained by CsA at 10 micromol/L in the K562/A02 cells. No effect on DNR sensitivity and retention was found in K562 cells (P > 0.05). CONCLUSION:
PSC 833 is at least 3 approximately 10 fold more potent than CsA or Ver with respect to MDR reversing activity, and it may function by inhibiting the function of P-gp and not reducing the levels of mdr1 mRNA and P-gp directly.
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Authors | Hui Dai, Shaokai Luo, Aihua Yin, Aihua Peng |
Journal | Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
(Zhonghua Xue Ye Xue Za Zhi)
Vol. 23
Issue 1
Pg. 23-6
(Jan 2002)
ISSN: 0253-2727 [Print] China |
PMID | 12015084
(Publication Type: Journal Article)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Calcium Channel Blockers
- Cyclosporins
- RNA, Messenger
- Cyclosporine
- Verapamil
- valspodar
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(drug effects, genetics, metabolism)
- Calcium Channel Blockers
(pharmacology)
- Cyclosporine
(pharmacology)
- Cyclosporins
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
- Humans
- K562 Cells
(cytology, drug effects, metabolism)
- RNA, Messenger
(drug effects, genetics, metabolism)
- Verapamil
(pharmacology)
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