Anti-tumor Effects of IL-1β Induced TRAIL-expressing hUCMSCs on Embelin on Treated Human Breast Cancer Cells.

• Main Authors: Jui-Wen Teng, 鄧睿文
• Other Authors: Hwai-Shi Wang
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/2b7q3b

碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 105 === Human umbilical cord Wharton’s jelly-derived mesenchymal stem/stroma cells (WJ-MSCs) have demonstrated high therapeutic value in cancer treatment owing to their ability of homing to cancer inflammation site. In addition, WJ-MSCs are less tumorigenic in comparison to bone marrow derived mesenchymal stem cells, a crucial difference which makes WJ-MSCs a better source for stem cell therapy. Our previous study has shown that pre-activating WJ-MSCs with cytokines promotes tumor necrosis factor-related apoptosis inducing ligand (TRAIL) expression and enhances cancer suppressive activity. Furthermore, increasing evidence indicate that embelin, an active extraction of Embelia ribes, induces apoptosis in several cancer cell lines via upregulated TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). This study was conducted to examine the effect of embelin on apoptosis and DR4 and DR5 expression of the MDA-MB-231 and MCF-7 breast cancer cell lines and to investigate potential mechanisms involved in apoptosis pathways. Whether IL-1β induced TRAIL-expressing WJ-MSCs, in combination with low-dose embelin, would further induce apoptosis in both breast cancer cell lines was also examined. In this study, MTT assay showed dose-dependent effect of embelin treatment ranging from 0 to 25μM in 24 and 48 hr. Western blotting and immunofluorescence staining were conducted to determine DR4 and DR5 expression after treatment with low-dose embelin. Additionally, embelin regulated caspase 8 or caspase 9 protein levels potentially leading to different apoptosis pathways were also examined. Moreover, flow cytometry confirmed that coculture of IL-1β activated hUCMSCs and embelin treated MDA-MB-231 enhances the apoptosis rate of MDA-MB-231. In conclusion, we suggest that embelin stimulated the expression of DR4 and DR5 in breast cancer cell lines, and that IL-1β activated WJ-MSC in combination with embelin inhibit MDA-MB-231 cells proliferation through TRAIL-related pathways.