Effect of Tamoxifen on the Multidrug-resistant Phenotype in Human Breast Cancer Cells: Isobologram, Drug Accumulation, and Mr 170,000 Glycoprotein (gp170) Binding Studies
1994
Abstract We have performed isobologram analyses of the ability of tamoxifen (TAM) to alter the response to Adriamycin (ADR) and vinblastine (VBL) in human breast cancer cells. MCF-7 cells express functional receptors for estrogen and progesterone but do not express detectable levels of M r 170,000 glycoprotein (gp170). CL 10.3 and MCF-7 ADR cells are MCF-7 variants which express gp170. CL 10.3 but not MCF-7 ADR cells express functional steroid hormone receptors. Tamoxifen (1–2.5 µ m) interacts synergistically with ADR and VBL in CL 10.3 and MCF-7 ADR cells. TAM increases the cytotoxicity of VBL and ADR and the intracellular levels of [ 3 H]VBL by approximately 2–3-fold. TAM also prevents the binding of [ 3 H]azidopine to gp170. The ability of TAM to concurrently increase the cytotoxic effects of ADR and VBL, increase VBL accumulation, and inhibit the binding of azidopine to gp170 strongly implies that the synergistic effects of TAM are mediated through its effects on gp170. TAM produces an antagonistic to additive interaction with ADR and VBL in MCF-7 cells, and at high concentrations (5 µ m) the synergy apparent in CL 10.3 and MCF-7 ADR cells is lost. While TAM clearly has a significant potential for use as a chemosensitizing agent, the design of clinical trials may require careful consideration. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
47
References
66
Citations
NaN
KQI