Evaluation Of DAPT On Triple Negative Cell Lines Enriching Breast Cancer Stem Cells In Vitro And Vivo

Objective :To investigate a novel way from DAPT to suppress triple negative breast cancer subpopulation with stem-cell-like properties. Methods:Triple negative breast cancer HCC38 cell lines was incubated in vitro. The cells with positive ALDH1 expression were isolated by ALDH sorted kits. These cells treated by Normal Saline, DAPT and Docetaxel were divided into vehicle group、observed group and positive control group.1.ALDH sorted kits were used to isolate the cells with positive ALDH1 expression from normal cells.2.Microspheres(MSs) formation was used to identify the exist of stem cells in HCC38 and HCC1806 cell lines.3.The viability of the HCC38 cell line was tested by MTT.4.DAPT to the effect of cell apoptosis was tested by Flow cytometry.5.Western blot test for detection of Notch1 protein levels.6.Transwell invasion assay proved tumor cell migration.7.HCC38 or HCC1806 were inoculated in nude mice, and the inhibitory effect of DAPT on tumor in nude mice was observed. Results:HCC 38 cells can form microspheres in serum-free culture conditions. Compared with vehicle group, DAPT can not only destruct spheres, and compared with Docetaxel, DAPT is more obvious. DAPT can not only inhibit the growth of HCC38 cells, induce apoptosis of HCC38, can also reduce the aggressivity, inhibit HCC38 cells protein expression. In vivo, DAPT can inhibit the growth of tumor in nude mice. Conclusion:DAPT, as the Notch signal transduction pathway inhibitor, can inhibit Notch downstream protein Notch1’s expression, and selectively kill breast cancer stem cells, may be of potential therapeutic value against triple-negative breast cancer with stem-cell-like properties.