Study the effect of IL-6 and BET inhibitor interaction on Cancer Stem Cell population in the human breast cancer cell lines MCF-7 and MDA-MB-231

Introduction& Aim: Breast cancer is the most common cancer in women around the world. Although significant advances have been made in breast cancer treatments, but some patients experience incurable metastatic disease. A subset of breast cancer cells termed as breast cancer stem cells (BCSCs), are responsible for cancer recurrence. BCSCs are able to self-renewal and they are more resistant to chemotherapy and radiotherapy. Also Interlukine (IL)-6 is one of the major tumor microenvironment in breast cancer that plays important role in activation of important signaling pathways in BCSCs. Recently, because of the role of epigenetic machinery in cancer biology, studies of cancer treatment have been attracted toward blocking components of gene expression regulators. (BET) proteins are one of the class of gene expression regulators that have crucial roles in cell cycle control and proliferation. (+)-JQ1 is a BET inhibitor that target BET proteins. In This study, we surveyed the effect of (+)-JQ1 on BCSCs population in MCF-7 and MDA-MB-231 cell lines.Methods: MCF-7 and MDA-MB-231cells that pre-treated with IL-6 for 2 weeks along with untreated cells were treated with JQ1 for 48 and 72h and cell viability was determined by MTT assay.For identification of CD44+/CD24-, cells were stained FITC-conjugated anti-CD24 and PE-conjugated anti-CD44 antibodies and were analyzed by using flow cytometry.Results: JQ1 had no effect on the inhibition of proliferation in MCF-7 and cell viability of all groups of MCF-7 cells was similar to control group(untreated), but in MDA-MB-231 IC50 value reached. The inhibitory effect of JQ1 alone on MDA-MB-231 after 48h and 72h was similar to each other and cell viability 50 percent decreased. Also combination treatment of IL-6 and JQ1 had the same result.Treatment with JQ1 has no effect on BCSCʹs population of any studied groups of MDA-MB-231 cells, while the population of BCSCs in MCF-7 cells under effect of JQ1 in presence of IL-6 and without it, has increased significantly. Unexpectedly treatment of MCF-7 cells with IL-6 decrease the population of BCSCs in comparison to untreated MCF-7 cellsconclusion: High concentration of JQ1 induced apoptosis in MDA-MB-231 cells and this is not suitable for cancer therapy. Stability of BET proteins exists in JQ1-resistant cells of MDA-MB-231 cell line and BET proteins became over-phosphorylate. Maybe combination therapy of JQ1 and drugs that dephosphorylate BET proteins can be effective. Also more studies should be done to understand the mechanism of effect of JQ1 on converting non-BCSCs to BCSCs in MCF-7 cells.

کلیدواژه ها:

breast cancer ، IL-6 ، BCSC