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RAPID UP-REGULATION OF MDR1 EXPRESSION BY ANTHRACYCLINES IN A CLASSICAL MULTIDRUG-RESISTANT CELL-LINE


HU, XF; SLATER, A; Wall, DM; Kantharidis, P; PARKIN, JD; Cowman, A; Zalcberg, JR
1995-05
BRITISH JOURNAL OF CANCER
Journal Article
71
5
931-936
Studies were carried out in a Variant human multidrug-resistant (MDR) cell line CEM/A7R, which expresses very low Levels of mdr1 mRNA and P-glycoprotein (P-gp). The induction of mdr1 RNA expression by three anthracyclines, (doxorubicin, daunorubicin, epirubicin), VP-16 and two vinca alkaloids (vincristine, vinblastine) was semiquantitatively assessed by scanning Northern blots on a phosphorimager. The relative level of mdr1 expression was expressed as ratio of mdr1 to the internal RNA (actin). A significant increase (P < 0.02) in expression of mdr1 was noted within 4 hrs of exposure to 1.5 mu g ml(-1) daunorubicin or epirubicin. Neither vinblastine nor vincristine had any effect on mdr1 levels after an 8 h exposure. With increasing concentrations of daunorubicin or epirubicin in a fixed 24 h time period, mdr1 expression increased, although a biphasic response was seen. Based on MRK 16 binding, an increase in P-gp levels was seen in the CEM/A7R line after a 24 h exposure to 1 mu g ml(-1) daunorubicin or epirubicin. The rapid increase in mdr1 expression after a short period of exposure to doxorubicin, daunorubicin or epirubicin suggests that induction of mdr1 expression may have an important role in the development of drug-resistant tumours.
STOCKTON PRESS
P-GLYCOPROTEIN; DRUG-RESISTANCE; HEAT-SHOCK; GENE PROMOTER; ACTIVATION; INDUCTION; LEUKEMIA; CHEMOTHERAPY; MODULATION; CARCINOMA
10.1038/bjc.1995.180
Refer to copyright notice on published article.

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Creation Date 1995-05-01 12:00:00