Suppression of multi-drug resistance gene expression in the mouse liver by 1,4-bis[2,(3,5-dichloropyridyloxy)]benzene

TY - JOUR

T1 - Suppression of multi-drug resistance gene expression in the mouse liver by 1,4-bis[2,(3,5-dichloropyridyloxy)]benzene

AU - Russell, Alison L.

AU - Henderson, Colin J.

AU - Smith, Gillian

AU - Wolf, C. Roland

PY - 1994/8/15

Y1 - 1994/8/15

N2 - 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 and 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 1, 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 induced 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. (C) 1994 Wiley-Liss, Inc.

AB - 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 and 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 1, 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 induced 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. (C) 1994 Wiley-Liss, Inc.

U2 - 10.1002/ijc.2910580417

DO - 10.1002/ijc.2910580417

M3 - Article

SN - 0020-7136

VL - 58

SP - 550

EP - 554

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 4

ER -