Anti-stem cell factor enhances the effect of Anthracycline and Taxane chemotherapy in chemoresistant breast cancer cell lines


Year:

Session type:

Neil Jelly, Issam Hussain, Suebwong Chuthapisith, Jenny Eremin, Oleg Eremin, Mohamed El-Sheemy

University of Lincoln, UK

Abstract

Proffered paper presentation

Introduction
Neoadjuvant chemotherapy is frequently used to treat locally advanced breast cancer (BC), to down grade the cancer, which may be compromised by cancer chemoresistance. Resistance to chemotherapy exposes patients to ineffective and expensive treatment with high morbidity. In BC cells overexpression of B Cell Lymphocyte-2 (Bcl-2) and low levels of annexin V relates to antiapoptotic activity and tumour proliferation. Extracellular protein expression of CD24 is a marker for Bcl.

Stem Cell Factor may be co expressed with Bcl-2, however; the relationship between Bcl-2 and Stem Cell Growth Factor (SCF) is poorly defined. In haematological cancer anti-stem cell factor (A-SCF) is widely used to enhance chemotherapy, but it is not used in solid cancer e.g., BC. The aim of this study, therefore, is to examine the CD24 expression and the effects of chemotherapeutic agents (e.g., Paclitaxel and Adriamycin) with SCF and A-SCF.

Method
Resistant cell lines Paclitaxel (MCF-7/PacRes), Adriamycin (MCF-7/AdrRes) and the wild type breast cancer cell line (MCF-7/WT) were cultured. Immunofluorescence and flow cytometry were used to analyse the expression of CD24 in these cell lines. Cells were treated with minimal lethal dose of chemotherapy either alone or combined with SCF and/or Anti-SCF and examined for both Bcl-2 and Annexin V proteins by ELISA.

Results
The expression of CD24 in MCF-7/AdrRes, MCF-7/PacRes and MCF-7/WT cells was (84%, 67% and 16%, respectively). There was significant over expression of Bcl-2 in the presence of SCF in MCF-7/AdrRes and MCF-7/PacRes cells compared with MCF-7/WT cells (76%, 35% and 13%, respectively). When anti-SCF was added in the presence or absence of SCF Bcl-2 expression was decreased significantly. After treatment with anti-SCF annexin V expression was significantly increased in MCF-7/AdrRes and MCF-7/WT cells (41% and 62%).

Conclusion
BC resistant cell lines show overexpression of CD24. SCF increases chemoresistance. Anti-SCF enhances the effect of chemotherapy.