Survivin inhibition induces human neural tumor cell death through caspase-independent and -dependent pathways

摘要: Survivin inhibits apoptosis during development and carcinogenesis is absent in differentiated cells. To determine whether survivin inhibition induces cell death neural tumor cells, antisense oligonucleotides (SAO) were administered to a human neuroblastoma (MSN) an oligodendroglioma (TC620) resulting dose-dependent reduction protein. Although 74% of the SAO-treated MSN cells trypan blue+, PARP cleavage or activated caspase-3 was not observed. However nuclear translocation AIF occurred XIAP increased dramatically. Co-administration z-Val-Ala-Asp(OMe)-fluoromethyl ketone (zVAD-fmk) with SAO did inhibit suggesting caspase-independent mechanism death. Propidium iodide (PI) staining revealed multiple large macronuclei no apoptotic bodies supporting role for division. By contrast, while 70% TC620 cleaved, TUNEL+ PI-staining numerous bodies. Co-treatment zVAD-fmk blocked While observed there two-fold increase metaphase Our results suggest that decreases viability as result mitotic catastrophe, can be initiated by either classic mechanism.