| Reversal of multidrug resistance by an immunosuppressive agent FK-506. | |
| | |
MedLine Citation:
|
PMID: 1370765 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
FK-506, a novel immunosuppressive agent, was examined for its reversing effect on multidrug-resistant tumor cells. FK-506 at 3 microM completely reversed the resistance against vincristine (VCR) in vitro in VCR-resistant mouse leukemia P388 cells (P388/VCR). FK-506 also enhanced the cytotoxicity of VCR in Adriamycin(ADM)-resistant human ovarian cancer A2780 cells (AD10) and ADM-resistant human myelogenous leukemia K562 cells (K562/ADM) in vitro. FK-506 was also effective in modulating sensitivity to ADM in AD10 cells in vitro. FK-506 enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When 20 mg/kg FK-506 was combined with 200 micrograms/kg VCR, a T/C value of 151% was obtained. Under the protocol used in this study, FK-506 was more potent than cyclosporin A (CsA) and verapamil. FK-506 inhibited [3H]azidopine binding to P-glycoprotein efficiently. The binding of VCR to K562/ADM plasma membrane was inhibited by FK-506 as effectively as by CsA. Moreover, the accumulation of VCR in AD10 cells was increased by FK-506 as efficiently as that of CsA and verapamil. These results indicate that FK-506 directly interacts with P-glycoprotein like CsA and verapamil, inhibits the active efflux of vincristine from resistant cells, increases the vincristine accumulation in resistant cells, and thus overcomes multidrug resistance in vitro and in vivo. |
| | |
Authors:
|
M Naito; T Oh-hara; A Yamazaki; T Danki; T Tsuruo |
Related Documents
:
|
9500455 - Role of glutathione s-transferases in the resistance of human colon cancer cell lines t... 8794885 - Bibw22 bs, potent multidrug resistance-reversing agent, binds directly to p-glycoprotei... 20053435 - The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamm... 9864175 - Efflux of rhodamine from cd56+ cells as a surrogate marker for reversal of p-glycoprote... 20508865 - Decreasing expression of the g1-phase inhibitors, p21cip1 and p16ink4a, promotes divisi... 454605 - The effect of cell excision and microelectrode perforation on membrane resistance measu... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cancer chemotherapy and pharmacology Volume: 29 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 1992 |
Date Detail:
|
Created Date: 1992-03-02 Completed Date: 1992-03-02 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: GERMANY |
Other Details:
|
Languages: eng Pagination: 195-200 Citation Subset: IM |
Affiliation:
|
Institute of Applied Microbiology, University of Tokyo, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antineoplastic Combined Chemotherapy Protocols / therapeutic use Cell Death / drug effects Cell Division / drug effects Doxorubicin / administration & dosage, pharmacology* Drug Resistance / genetics* Drug Synergism Female Humans Leukemia Leukemia P388 / drug therapy Membrane Glycoproteins / antagonists & inhibitors Ovarian Neoplasms P-Glycoprotein Tacrolimus / administration & dosage, pharmacology* Tumor Cells, Cultured / drug effects*, metabolism Vincristine / administration & dosage, pharmacology* |
| Chemical | |
Reg. No./Substance:
|
0/Membrane Glycoproteins; 0/P-Glycoprotein; 109581-93-3/Tacrolimus; 23214-92-8/Doxorubicin; 57-22-7/Vincristine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Splenic and inguinal lymph node T cells of aged mice respond differently to polyclonal and antigen-s...
Next Document: Effect of tolmetin sodium dihydrate on adhesion formation by intraperitoneal administration of antin...