Abstract 527: Pyrrole-Imidazole polyamide inhibits MMP-9 transcription and induces suppression of tumor metastasis

Abstract Pyrrole-Imidazole (PI) polyamide that targets the AP-1-binding site of the MMP-9 promoter was designed and synthesized as a gene-silencing agent for tumor metastases. MMP-9, the 92-kDa type IV collagenase, contributes to tumor invasion and metastases, and strategies to down-regulate its expression could ultimately be of clinical utility. The synthesized MMP-9 PI polyamide showed selective DNA binding ability and significantly inhibited MMP-9 mRNA and protein expression and enzymatic activity in both MDA-MB-231 and Hela cells. Furthermore, the MMP-9 PI polyamide inhibited migration and invasion by in vitro wound-healing and matrigel-invasion assay. The FITC-labeled PI polyamide was localized in nuclei in 45 minutes of incubation with an MDA-MB-231 cell and remained in the nuclei up to 96 hours after incubation in vitro. It was also quickly localized in the mouse cellular nuclei of many tissues, including liver, kidney and spleen, after intravenous injection without using any drug-delivery system. Moreover, the polyamide treatment significantly decreased metastasis of xenografted tumor cells and host angiogenesis in tumors in a mouse model of liver metastasis. Our results suggest that this PI polyamide that targets the MMP-9 gene promoter can be a novel MMP-9 down-regulating molecule for anti-metastasis. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 527.