Abstract |
The present study demonstrated that poly(oxypropylene) and poly(oxyethylene) block copolymer pluronic L61 (L61)-hypersensitized multidrug-resistant CHRC5 Chinese hamster ovary cells and MCF-7/ADR human breast carcinoma cells to the cytotoxic action of doxorubicin (Dox). CHRC5 and MCF-7/ADR cells manifested 290- and 700-fold increases, respectively, in their sensitivity to Dox/L61 formulation compared with free Dox. Their sensitive counterparts Aux-B1 and MCF-7 displayed only marginal or no increase at all in their response to Dox/L61. The study of the drug transport performed by flow cytometry showed that L61 enhanced the drug uptake and reduced the P-glycoprotein-mediated drug efflux. Visualization of Dox subcellular distribution in CHRC5 cells by fluorescent microscopy revealed that Dox was sequestered in cytoplasmic vesicles, whereas incubation of the cells with Dox/L61 altered the drug compartmentalization by releasing the drug from these vesicles and shifting it to the nucleus. These findings suggested that the hypersensitive response of multidrug-resistant cells to the action of Dox/L61 was caused by an increase in the drug accumulation and changes in its subcellular distribution.
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Authors | A Venne, S Li, R Mandeville, A Kabanov, V Alakhov |
Journal | Cancer research
(Cancer Res)
Vol. 56
Issue 16
Pg. 3626-9
(Aug 15 1996)
ISSN: 0008-5472 [Print] United States |
PMID | 8705995
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antibiotics, Antineoplastic
- Polymers
- Doxorubicin
- Poloxalene
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(physiology)
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Biological Transport
- CHO Cells
- Cricetinae
- Doxorubicin
(administration & dosage, pharmacokinetics, pharmacology)
- Drug Resistance, Multiple
- Female
- Humans
- Poloxalene
(pharmacology)
- Polymers
(pharmacology)
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