Document Detail


Effect of short-term morphine exposure on P-glycoprotein expression and activity in cancer cell lines.
MedLine Citation:
PMID:  15069552     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multidrug resistance (MDR) is a common problem in various types of cancer. One important factor in the development of MDR is overexpression of P-glycoprotein, encoded by the MDR1 gene. Morphine is the opioid of choice for moderate to severe cancer pain, and is a substrate of P-glycoprotein. Recently, morphine has been shown to induce P-glycoprotein expression in the rat brain. Using Western blot analysis and cytotoxicity assays respectively, we have investigated the effects of short-term (72 h) morphine treatment on P-glycoprotein expression in a panel of human cancer cell lines, and its effects on cellular resistance to the known P-glycoprotein substrates, vinblastine and colchicine. The effect of morphine on P-glycoprotein expression and activity in the mouse fibroblast NIH-3T3 cell was assessed to establish whether morphine effects are species specific. Short-term exposure to morphine did not result in any significant differences in P-glycoprotein expression or activity in any cancer cell lines. Morphine pre-treatment resulted in a moderate but significant increase in sensitivity of NIH-3T3 cells to vinblastine, but not colchicine. This study suggests that morphine effects may be cell-type specific. Importantly, however, it appears that short-term morphine treatment does not affect the MDR phenotype of tumour cells.
Authors:
Marina Pajic; Mary Bebawy; Janelle M Hoskins; Basil D Roufogalis; Laurent P Rivory
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  11     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-04-07     Completed Date:  2004-11-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1091-5     Citation Subset:  IM    
Affiliation:
Children's Cancer Institute of Australia for Medical Research, Randwick, Sydney, NSW 2031, Australia. mpajic@ccia.org.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cell Survival / drug effects
Colchicine / toxicity
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Mice
Morphine / pharmacology*
P-Glycoprotein / metabolism*
Vinblastine / toxicity
Chemical
Reg. No./Substance:
0/P-Glycoprotein; 57-27-2/Morphine; 64-86-8/Colchicine; 865-21-4/Vinblastine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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