Embryonic Stem Cells Derived Exosomes Enhances Chemosensitivity of Doxorubicin in Breast Cancer Cells

Abstract

Doxorubicin (DOX) is the most effective anti‐tumor agent to treat wide variety of solid tumors, including the breast cancer. However, it is not known whether combination treatment of embryonic stem cells derived exosomes (ES‐exos) with DOX influences the killing of breast cancer cells. To address this question, breast cancer cell lines, MDA‐MB231 and MCF7 were treated with DOX (1mM) ± ES‐exos (5 μg/ml, 10 μg/ml or 20 μg/ml) for 24 and 48 hrs. Cell death was assessed by trypan blue exclusion assay and cell proliferation was measured by MTS assay. DOX treatment of MDA‐MB‐231 cells caused significant increase in cell death at 48 hrs post treatment, from 11.4 ± 0.01 in non‐treated controls to 38.2 ±1.2 % (p<0.05, n=4; Figure 1A). However, combinatorial treatment with DOX and ES‐exos increased cell death to 49.2± 2.1% (p<0.05 vs DOX, n=4; Figure 1A). Identical results were obtained when MCF‐7 cells were treated with DOX ± ES‐exos (Figure 1B), although these cells were relatively less sensitive to cell death compared to the MDA‐MB231 cells. Similarly, co‐treatment with ES‐exos resulted in an additive effect on DOX‐induced reduction of proliferation in both cell lines. Treatment of cancer cell lines with ES‐exos alone (concentrations ranging from 5 μg/ml to 20 μg/ml) had no significant effect on cell death or proliferation. These results suggest that ES‐exos dramatically sensitize the cell killing effect of DOX in breast cancer cells which may translate to enhancing the anti‐tumor properties of DOX. We also identified 30 to 400 fold increase in miR‐96, miR‐124, miR‐200a, b, c, miR‐205, MiR‐211 in ES‐exos compared with MEF‐exos (exosome isolated from non‐ES cells) (Figure 1C). Further investigations are in progress to demonstrate the functional role of the miRs or their protein targets in enhancing the chemosensitivity of DOXSupport or Funding InformationRO1CA221813 Figure 1This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.