Abstract

Tamoxifen is the most commonly used drug in the treatment of breast cancer via blocking the estrogen receptor pathway.
However, the use of Tamoxifen is limited by intrinsic and acquired resistance, which may be associated with the de-regulation
of the kinase protein expression or an increase in multiple drug resistance (MDR) expression. Two breast cancer cell lines, wild
type MCF7 WT (sensitive, i.e., ER+
) and MDA-MB-231 (resistant, i.e., ER-
), were used. Expression of P-glycoprotein (Pgp)
was measured, the cells were treated with 4- hydroxy tamoxifen in the presence or absence of anti-stem cell factor, apoptosis
protein (Annexin V) was measured and Influx/efflux rates were monitored by using Technetium99m methoxyisobutylisonitrile
(
99m Tc-Sestamibi-MIBI) at different time intervals. Results showed positive expression of AnnexinV in MDA-MB-231 and
MCF7/WT, and the effect of blocking of the stem cell factor showed an increase in the drug accumulation within the MDAMB-231 cell line. In conclusion, this study showed that the anti-stem cell factor enhances the effectiveness of antihormonal
therapies determined by 99m Tc-MIBI. These findings may have implications for the use of anti-stem cell factor with antihormonal therapy in ER-negative breast cancer in order to overcome drug resistance and improve the outcome.