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Suppression of multi‐drug resistance gene expression in the mouse liver by 1,4‐bis[2,(3,5‐dichloropyridyloxy)]benzene
Author(s) -
Russell Alison L.,
Henderson Colin J.,
Smith Gillian,
Roland Wolf C.
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580417
Subject(s) - p glycoprotein , multiple drug resistance , cytochrome p450 , gene , context (archaeology) , hormone , gene expression , biology , glycoprotein , pharmacology , drug resistance , inducer , cancer research , in vivo , function (biology) , medicine , endocrinology , microbiology and biotechnology , biochemistry , metabolism , genetics , paleontology
Abstract P‐glycoproteins encoded by the (multi‐drug resistance) mdr genes play a central role in the resistance of tumor cells to a wide range of anti‐cancer drugs. Modulation of P‐glycoprotein function could therefore provide a means of sensitising tumor cells to chemotherapy. Studies in this context have centred around the use of compounds which antagonise the P‐glycoprotein membrane transport system. To investigate the possibility of modulating P‐glycoprotein expression at a transcriptional level, we investigated the effects of hormonal factors and cytochrome P450‐inducing agents on hepatic expression of murine mdr I, mdr 2 and mdr 3. Hepatic mdr 2 and mdr 3 expressions were significantly suppressed in hypophysectomised animals, indicating that pituitary hormones activate the hepatic expression of these genes. Many of the foreign compounds and anti‐cancer drugs tested did not significantly induce mdr 1, 2 or 3 expression. However, it was of particular interest that a potent cytochrome P450 inducer, 1,4‐bis[2‐(3,5‐dichloropyridyloxy)]benzene, almost completely suppressed hepatic mdr 2 and 3 expressions.