Targeting of Survivin Inhibits Neuroblastoma Cell Proliferation

Poster #65

High-risk neuroblastoma (NB) is an aggressive pediatric tumor which develops from the extracranial sympathetic nervous system and accounts for almost 15% of all childhood cancer-related deaths. Survivin is known to be involved in controlling cell division and apoptosis and belongs to the inhibitor of apoptosis protein family. Oncogenic activation of survivin has been reported in different cancers including NB. In the present study, we analyzed genomic datasets of 1135 NB patients and found that high expression of survivin coding gene BIRC5 strongly correlates with poor overall and event-free survival of NB patients. More aggressive tumors have significantly higher BIRC5 levels. To understand the effects of inhibiting survivin on NB growth, we used a specific small molecule inhibitor and found that survivin inhibition significantly inhibit NB cell proliferation, colony growth, blocks cell cycle progression, induce apoptosis, and inhibit 3D spheroid tumor formation and growth in a dose-dependent manner. Overall, our data highlights the importance of survivin as a target in NB, and the potential of survivin inhibition as a novel therapeutic approach for NB. In our future efforts, we will combine the survivin inhibitor with chemotherapy drugs such as doxorubicin to develop a less-toxic and more-effective therapeutic approach for NB.

Authors
Danielle C. Rouse
Rameswari Chilamakuri
Bharti Sharma
Saurabh Agarwal

Mentor
Dr. Saurabh​​​​​​​ Agarwal
Pharmaceutical Sciences
College of Pharmacy and Health Sciences

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