Abstract 351: A targeted nanocomplex of the IKBKE siRNA inhibits invasiveness and growth of triple negative breast cancer cells

Abstract

Abstract IκB kinase ϵ (IKBKE, or known as IKKϵ), an important mediator in the activation of NF-κB pathway, was recently identified as an oncogene in breast cancer and overexpressed in approximately 30% of breast carcinomas. It is also highly expressed in TNBC cells, which is correlated with angiogenesis process, high metastasis in NF-κB pathway of TNBC. We found that silencing IKBKE in TNBC cells using siRNA significantly inhibits the proliferation, migration and invasion of TNBC cells by specific silenced 71% of IKBKE in vitro. In vivo study indicated that IKBKE siRNA can inhibit TNBC tumor growth after peritumoral injection at a IKBKE siRNA dose of 0.3 mg/kg. We next developed a CD44-targeting, cholesterol-peptide based nanocomplex to co-deliver the IKBKE siRNA and cabazitaxel to TNBC cells. The nanocomplex showed the synergistic effect of the IKBKE siRNA and cabazitaxel on inhibiting the growth of TNBC tumors in vivo. Modification of the nanocomplex with CD44 further improved tumor uptake and anti-tumor efficacy of the nanocomplex. Our results suggest that IKBKE siRNA is a promising anti-tumor agent for TNBC therapy, and co-delivery of IKBKE siRNA and cabazitaxel using a CD44-targeting nanocomplex is a potential strategy for TNBC treatment. Moreover, this multifunctional delivery system provides a platform for other combination therapy including an siRNA and a chemotherapy drug. Citation Format: Zhen Zhao, Yuanke Li, Kun Cheng. A targeted nanocomplex of the IKBKE siRNA inhibits invasiveness and growth of triple negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 351.