199 Novel Functions of Cyclin A2 in Epithelial-Mesenchymal Transition and Metastasis

Materials and Methods:We have developed a bi-specific and bi-functional RNA/DNA oligonucleotide to target both a and a′ catalytic subunits of CK2 (termed RNAi-CK2) encapsulated in the tenfibgen (TBG) protein shell to treat prostate and head neck tumors in xenograft models. Use of this nanocapsule in cell culture experiments has been previously reported; here we report on its use in xenograft models of human cancer in mice. Results: Systemic delivery of TBG-RNAi-CK2 nanocapsules resulted in decreased orthotopic prostate tumor size in conjunction with downregulation of CK2 expression after only 2 treatments; additionally, significantly reduced metastatic lymph node tumor volume was observed. Likewise, treatment of head neck xenograft tumors at very low doses resulted in caspase 7 activation and tumor shrinkage; whereas treatment at high doses resulted in up to 75% 6-month survival in multiple head neck cancer models. Comparative studies using the TBG nanoencapsulation technology for therapeutic delivery of the CK2 small molecule inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) versus RNAi-CK2 in prostate cancer will also be presented. Finally, biodistribution studies showed that TBG nanoencapsulation imparted tumor specific accumulation in primary, metastatic and bone-located tumors but no accumulation in non-tumor tissues. Conclusions: We propose that delivery of the bi-specific RNA/DNA chimeric oligonucleotide directed against CK2 using TBG nanocapsules may be uniquely useful for cancer therapy. Supported by grants from Department of Veterans Affairs, National Cancer Institute and National Institutes of Health.