Rapid up-regulation of mdrl expression by anthracyclines in a classical multidrug-resistant cell line

X. F. Hul, A. Slater, D. M. Wall, P. Kantharidis, J. D. Parkin, A. Cowman, J. R. Zalcberg

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Abstract

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 micrograms 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 microgram 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.

Original languageEnglish
Pages (from-to)931-936
Number of pages6
JournalBritish Journal of Cancer
Volume71
Issue number5
DOIs
Publication statusPublished - 1995
Externally publishedYes

Keywords

  • Anthracycine resistance
  • Drug resistance
  • Induction of mdrl

Cite this

Hul, X. F. ; Slater, A. ; Wall, D. M. ; Kantharidis, P. ; Parkin, J. D. ; Cowman, A. ; Zalcberg, J. R. / Rapid up-regulation of mdrl expression by anthracyclines in a classical multidrug-resistant cell line. In: British Journal of Cancer. 1995 ; Vol. 71, No. 5. pp. 931-936.
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Rapid up-regulation of mdrl expression by anthracyclines in a classical multidrug-resistant cell line. / Hul, X. F.; Slater, A.; Wall, D. M.; Kantharidis, P.; Parkin, J. D.; Cowman, A.; Zalcberg, J. R.

In: British Journal of Cancer, Vol. 71, No. 5, 1995, p. 931-936.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Rapid up-regulation of mdrl expression by anthracyclines in a classical multidrug-resistant cell line

AU - Hul, X. F.

AU - Slater, A.

AU - Wall, D. M.

AU - Kantharidis, P.

AU - Parkin, J. D.

AU - Cowman, A.

AU - Zalcberg, J. R.

PY - 1995

Y1 - 1995

N2 - 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 micrograms 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 microgram 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.

AB - 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 micrograms 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 microgram 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.

KW - Anthracycine resistance

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