Abstract
Abstract Survivin, a protein highly expressed in human cancers is involved in both control of cell cycle progression and inhibition of apoptosis. Transcription of the survivin gene locus (BIRC-5) yields at least 5 alternative splice variants including survivin wild-type (WT), survivin ΔEx3, survivin 2B, survivin 3B, and survivin 2α. Here, we studied the role of survivin and its splice variants in taxane-resistant ovarian cancer. Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared to sensitive cells. Small-interference RNAs (siRNAs) targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA). Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B siRNA incorporated into DOPC nanoliposomes resulted in significant reduction in tumor growth (p<0.05) in the HeyA8.MDR and SKOV3.TR models, and these effects were similar to T-siRNA-DOPC. The anti-tumor effects were further enhanced in combination with docetaxel chemotherapy (p<0.01). Finally, we found a significant association between survivin 2B expression and progression free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery. These data identify survivin 2B as an important target in ovarian cancer, and provide a translational path forward for developing new therapies against this target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1735. doi:10.1158/1538-7445.AM2011-1735
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