Indication indused cancer stem cells with vincristine and designate of drug sensibility in gastric cell lines

In recent years, cancer stem cells (CSCs) have come into focus in cancer treatment studies and tumor angiogenesis and it is an important target for cancer therapy. CSCs have self-renewal and pluripotent capacity. Vincristine is widely used as a chemoterapic anticancer drug to treat various cancers. Nevertheless, recent research about Vincristine indicates that it can distinguish between cancer cells and cancer stem cells. Tumor angiogenesis has also been reported to be related to CSC survival and chemoterapic drug resistance. The Notch pathway plays a critical role in cellular differentiation, survival and angiogenesis and in this pathway DLL4 ligand is as a key player in angiogenesis. Based on these, for the first time we searched for the effect of Vincristine and blockage of Notch pathway with anti DLL4 antibody in AGS gastic cancer cell line. Cytotoxicity of Vincristine and anti DLL4 on AGS cell line was determined by MTT analysis. Cancer stem cells in AGS cell population were selected following the application of Vincristine. The morfology, colonization, spheroid formation and differentiation of the selected cells were analyzed. Then, Anti DLL4 antibody was used to block Notch pathway by inhibiting DLL4 ligand to see whether vessel like structures are reversed in anti DLL4 treated AGS cells compaired to the untreated control AGS cells. Finally, the combined effect of vincristine and anti DLL4 on vessel like structure formation was determined on cancer stem cell like AGS cells.