Abstract 1753: XIAP maintains the characteristics of cancer stem cells and is a therapeutic target in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a common malignancy in South China. Cancer stem cells (CSCs) are thought as the key players in the resistance to chemo- or radio-therapy and are response for tumor recurrence and metastasis, while their ability to escape from the apoptosis pathway may render them the resistant property to the therapies. We show that XIAP is overexpressed in the NPC cell line S18, which have the higher SP populations and CD44+ populations and the stronger abilities of sphere-formation and metastasis. Importantly, XIAP knockdown decreases SP and CD44+ populations, prevents sphere-formation and reduces the ability of invasion and migration. What more, loss of XIAP enhances the sensitivity of cells to conventional chemotherapy drugs CDDP and 5-FU. The primary xenograft tumor formation in vivo found there is a dramatic reduction in tumor formation in the XIAP KD group. They all indicate that XIAP plays an important role in nasopharyngeal cancer stem cell. Further studies show that XIAP limits MAPK signaling and thereby restricts differentiation and maintains the characteristics of cancer stem cells. We designed and synthesized a novel Smac mimetic compound APG-1387 that promotes the rapid degradation of cIAP1/2 and XIAP, and it exerts an antitumor effect on nasopharyngeal carcinoma cancer stem cells. Further studies show that APG-1387 enhances the chemosensitivity and promotes apoptosis in combination with CDDP and 5-FU of NPC in vitro and vivo. Citation Format: jiao ji, Rong Deng, Wen-Dan Chen, Gong-Kan Feng, Xiao-Feng Zhu, Da-Jun Yang. XIAP maintains the characteristics of cancer stem cells and is a therapeutic target in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1753. doi:10.1158/1538-7445.AM2015-1753