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 Infux/efux rates were monitored by using Technetium 99m methoxyisobutylisonitrile ( 99m Tc-Sestamibi-MIBI) at diferent time intervals. Results showed positive expression of AnnexinV in MDA-MB-231 and MCF7/WT, and the efect of blocking of the stem cell factor showed an increase in the drug accumulation within the MDA- MB-231 cell line. In conclusion, this study showed that the anti-stem cell factor enhances the efectiveness of antihormonal therapies determined by 99m Tc-MIBI. These fndings may have implications for the use of anti-stem cell factor with anti- hormonal therapy in ER-negative breast cancer in order to overcome drug resistance and improve the outcome. Keywords: Antibody, Antihormonal therapy, Human breast cancer. International Journal of Drug Delivery Technology (2019); DOI: 10.25258/ijddt.9.4.15 How to cite this article: Arif, K.B., Hussain, I., Rea, C. and El-Sheemy, M. (2019). Stem Cell Factor Antibody: Efective Manipulation of Antihormonal Therapy in Resistant Human Breast Cancer In Vitro. International Journal of Drug Delivery Technology, 9(4): 608-612. Source of support: Nil. Confict of interest: None Stem Cell Factor Antibody: Efective Manipulation of Antihormonal Therapy in Resistant Human Breast Cancer In Vitro Khalid Bahram Arif, 1,2 Issam Hussain, 1 Carol Rea, 1 Mohamed El-Sheemy 3 1 School of Life Sciences, University of Lincoln, Brayford Pool, UK. 2 College of Medicine, Kirkuk University, Kirkuk , Iraq. 3 Lincoln County Hospital, Greetwell Road, Lincoln, Lincolnshire, UK. Received: 17th Oct, 19; Revised: 16th Nov, 19, Accepted: 15th Dec, 19; Available Online: 25th Dec, 2019 INTRODUCTION Breast cancer is the most commonly diagnosed disease and the leading cause of cancer death in women worldwide. 1 Tamoxifen is still the therapy of choice for ER + breast cancer. However, over 30% of breast cancer patients with ER + fail to respond to tamoxifen, whereas the responding patients may fnally progress to a resistant phenotype. 2,3 Despite the signifcant improvements in cancer treatment, resistance to therapeutic agents still represents a signifcant issue for optimal clinical management, partially due to the decrease in intracellular drug accumulation, i.e., increase the efux rate. 4,5 In breast cancer, a signifcant correlation was indicated between intercellular drug accumulation and acquired resistance to tamoxifen. Studies suggested an association between the presence of P-glycoprotein (Pgp) and inefective therapeutic medication resulting in poor prognosis. Therefore, Pgp expression might play a role in tamoxifen resistance. 6-8 On the other hand, Previous studies showed evidences of the role of the signaling transduction pathways such as RESEARCH ARTICLE mitogen-activated protein kinase (MAPK), c-Jun NH2- terminal kinase (JNK), p38, cyclic adenosine monophosphate- dependent protein kinase, phosphatidylinositol 3-kinase and protein kinase C signaling pathways in the regulation of the ATP-binding cassette (ABC) transporters. 9 The ABC proteins are part of the largest family of transmembrane proteins. These proteins function as energy-dependent and transport a variety of molecules/substrates across cellular membranes. 10 The expression of these transport proteins is implicated in pumping the drugs out of the cells, which prevents intracellular anticancer drug accumulation. This drug accumulation causes the development of multiple drug resistance (MDR), which is considered as one of the cellular pathways involved in resistance to anticancer drugs. These protein transporters include ABCB1 (P-glycoprotein), ABCC1 (MRP1), ABCC2 (MRP2), ABCC4 (MRP4), ABCG2 (BCRP) and the lung resistance protein (LRP). 11,12 To provide the basis for more efective combined molecular/ endocrine therapy regimen in breast cancer patients, many eforts have been made for better understanding of tamoxifen *Author for Correspondence: karif@uokirkuk.edu.iq brought to you by CORE View metadata, citation and similar papers at core.ac.uk provided by University of Lincoln Institutional Repository