Abstract 4736: Inhibition of STAT3 sensitizes neuroblastoma xenografts cells to Etoposide

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for more than 7% of malignancies in patients younger than 15 years and causing 10% of all pediatric oncology deaths. Chemoresistance remains a major obstacle to the successful treatment of high-risk NB patients. Since STAT3 is a determinant of chemoresistance and associated with tumor recurrence in several adult tumor model systems, we investigated the biologic consequences of targeting STAT3 in neuroblastoma. Using a Tet-inducible STAT3 shRNA in 3 representative NB cell line models (AS, NGP and IMR32), inhibition of constitutively activated STAT3 (P-STAT3) in NB cells statistically decreased cell proliferation, colony formation and motility as defined by a wound healing assay. NB cell lines with decreased P-STAT3 exhibited increased sensitivity to cisplatin and etoposide-induced cell death (EC50 in each cell line decreased 52% to 80% compared with parental cell lines) which could be partially rescued by caspase inhibitor Z-VAD. In vivo, STAT3 inhibition by Tet-inducible STAT3 shRNA in AS had little effect on tumor growth and survival in tumor-bearing mice, however the combination of STAT3 inhibition with etoposide significantly decreased tumor growth and increased the survival of tumor-bearing mice (P=0.009). Our study supports the development of strategies targeting STAT3 inhibition in combination with conventional cytotoxic therapy for patients with high-risk NB. Citation Format: Shuang Yan, Carol Thiele. Inhibition of STAT3 sensitizes neuroblastoma xenografts cells to Etoposide. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4736. doi:10.1158/1538-7445.AM2014-4736