Drug extrusion, 125I- efflux and the control of intracellular [Ca2+] in drug-resistant ovarian epithelial cells

H. L. Mcalroy, Douglas Bovell, J. A. Plumb, P. Thompson, S. M. Wilson

Research output: Contribution to journalArticle

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Abstract

Experiments were undertaken using an ovarian adenocarcinoma cell line (A2780) and a drug-resistant strain (A2780.ad) derived from this line. P-glycoprotein could not be detected in A2780 cells but was essentially ubiquitous in A2780.ad cells, although removing the selective pressure for drug resistance led to reduced expression. However, the amount of P-glycoprotein present was used to predict the capacity of these cells to extrude rhodamine-123 (R-123) and their resistance to adriamycin, a cytotoxic drug. This accords with the role of P-glycoprotein as a drug pump. Although hypotonic solutions increased anion efflux from A2780 and A2780.ad cells, larger responses occurred in the parental line. Moreover, R-123 extrusion and anion efflux appeared to be mutually independent processes and so these data do not support the view that P-glycoprotein is involved in the control of volume-sensitive anion channels. Hypotonic solutions increased intracellular free calcium ([Ca2+](i)) in drug-resistant cells but not in the parental line, and so establishing a drug-resistant strain may affect the control of [Ca2+](i) during osmotic swelling. This could account for effects that were previously attributed to P-glycoprotein.

Original languageEnglish
Pages (from-to)285-297
Number of pages13
JournalExperimental Physiology
Volume84
Issue number2
Publication statusPublished - Mar 1999
Externally publishedYes

Fingerprint

P-Glycoprotein
Epithelial Cells
Hypotonic Solutions
Anions
Pharmaceutical Preparations
Rhodamine 123
Drug Resistance
Doxorubicin
Adenocarcinoma
Calcium
Cell Line

ASJC Scopus subject areas

  • Physiology

Cite this

Drug extrusion, 125I- efflux and the control of intracellular [Ca2+] in drug-resistant ovarian epithelial cells. / Mcalroy, H. L.; Bovell, Douglas; Plumb, J. A.; Thompson, P.; Wilson, S. M.

In: Experimental Physiology, Vol. 84, No. 2, 03.1999, p. 285-297.

Research output: Contribution to journalArticle

Mcalroy, H. L. ; Bovell, Douglas ; Plumb, J. A. ; Thompson, P. ; Wilson, S. M. / Drug extrusion, 125I- efflux and the control of intracellular [Ca2+] in drug-resistant ovarian epithelial cells. In: Experimental Physiology. 1999 ; Vol. 84, No. 2. pp. 285-297.
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