| Reversal of P-glycoprotein-mediated multidrug resistance in vitro by doramectin and nemadectin. | |
| | |
MedLine Citation:
|
PMID: 20487225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVES: Multidrug resistance (MDR) is a serious obstacle encountered in cancer treatment. This study was performed to explore the reversal of MDR by doramectin from the avermectin family and nemadectin belonging to the milbemycin family. METHODS: The MTT assay was used to evaluate the abilities of the two compounds to reverse drug resistance in adriamycin-resistant human breast carcinoma cells (MCF-7/adr). Intracellular accumulation of adriamycin was determined by HPLC. The effects of the two compounds on inhibiting P-glycoprotein (P-gp) efflux was demonstrated by accumulation of rhodamine 123 in MCF-7/adr cells. To investigate the mechanism of reversal by the two compounds, the expressions of P-gp and the MDR1 gene encoding P-gp were tested by flow cytometry and reverse-transcriptase PCR. KEY FINDINGS: Doramectin and nemadectin at the high dose of 8 mumol/l significantly increased the sensitivity of MCF-7/adr cells to adriamycin by 49.35- and 23.97-fold, respectively. They also increased the intracellular accumulation of adriamycin and rhodamine 123 in MCF-7/adr cells in a dose-dependent manner. Expression of both P-gp and MDR1 were down-regulated. CONCLUSIONS: Doramectin and nemadectin are promising agents for overcoming MDR in cancer therapy. Doramectin was more potent in reversing MDR. |
| | |
Authors:
|
Aili Gao; Xiangjing Wang; Wensheng Xiang; Hongsheng Liang; Jiguo Gao; Yijun Yan |
Related Documents
:
|
9607955 - P-glycoprotein (p-gp) mediated efflux in caco-2 cell monolayers: the influence of cultu... 20121715 - Induction of apoptosis by a3 adenosine receptor agonist n-(3-iodobenzyl)-adenosine-5'-n... 9500455 - Role of glutathione s-transferases in the resistance of human colon cancer cell lines t... 8810535 - Intracellular ph does not affect drug extrusion by p-glycoprotein. 17706645 - Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional re... 15838515 - Biochemical and cellular mechanisms of mammalian cdk inhibitors: a few unresolved issues. |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: The Journal of pharmacy and pharmacology Volume: 62 ISSN: 2042-7158 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2010 Mar |
Date Detail:
|
Created Date: 2010-05-21 Completed Date: 2010-09-10 Revised Date: 2011-09-13 |
Medline Journal Info:
|
Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: England |
Other Details:
|
Languages: eng Pagination: 393-9 Citation Subset: IM |
Affiliation:
|
School of Life Science, Northeast Agricultural University, Harbin, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Absorption
/
drug effects Antibiotics, Antineoplastic / pharmacokinetics, pharmacology* Breast Neoplasms / drug therapy, metabolism Carcinoma / drug therapy, metabolism Cell Line, Tumor Cell Survival / drug effects Doxorubicin / pharmacokinetics Drug Resistance, Multiple / drug effects* Drug Resistance, Neoplasm / drug effects* Female Gene Expression Regulation, Neoplastic / drug effects Genes, MDR Humans Inhibitory Concentration 50 Ivermectin / analogs & derivatives*, pharmacology Macrolides / pharmacology* P-Glycoprotein / genetics, metabolism* RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Rhodamine 123 / pharmacokinetics |
| Chemical | |
Reg. No./Substance:
|
0/ABCB1 protein, human; 0/Antibiotics, Antineoplastic; 0/Macrolides; 0/P-Glycoprotein; 0/RNA, Messenger; 102130-84-7/nemadectin; 117704-25-3/doramectin; 23214-92-8/Doxorubicin; 62669-70-9/Rhodamine 123; 70288-86-7/Ivermectin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Anti-inflammatory effect of enzymatic hydrolysate of corn gluten in an experimental model of colitis...
Next Document: Comprehensive dentistry.