Research of caspase-8 and Bcl-2 on TRAIL resistance in brain tumor stem cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To detect the effect of TRAIL on the growth of brain tumor stem cells, study the role of Caspase-8 and Bcl-2 of TRAIL resistance. METHODS: Brain tumor stem cells were isolated by CD133 magnetic sorting, and the positive rates of CD133+ cells were detected by flow cytometry, the self-renewing capicity of brain tumor stem cells was examined by subneurosphere formation assay, and the percentage of cell death were examined by MTS assay, the expression of DR5, FADD, Caspase-8 and Bcl-2 proteins was detected by Western blot. RESULTS: The positive rates of CD133+ cells were 71% after CD133 magnetic sorting. Brain tumor stem cells grow as neurosheres and have the abilities to reform neuroshperes, the capacity of neurosphere formation was significant increased after TRAIL treatment or not. Brain tumor stem cells were dead after TRAIL treatments, Caspase-8 and Caspases inhibitor can block the cell death that induced by TRAIL (P < 0.05). The expression of Caspase-8 protein was decreased and Bcl-2 protein was increased in brain tumor stem cells (P < 0.05). CONCLUSION: Brain tumor stem cells may response to TRAIL resistance, the reason is the lower expression of Caspase-8 protein and over expression of Bcl-2 protein which is unable to activate Caspase-8.