Abstract A1-26: Inhibiting stemness and invasion property of glioma stem cells by biguanide compound

Abstract

Abstract Introduction: Ever since pharmacoepidemiologic clues of antineoplastic actions of metformin were reported in 2005, potential application of biguanide for the treatment of several types of cancer has been evaluated. To overcome limited pharmacokinetic properties of prototype biguanides such as metformin and penformin, a newly developed biguanide compound HL156A was developed. In the present, we assessed the potential biologic effect of HL156A on the glioma stemness and invasion properties. Methods: Using patient derived glioma cancer stem cells (gCSCs), we assessed cell viability, AMPK-mTOR pathway, stemness, differentiation, tumor invasion and epithelial-mesenchymal properties of gCSCs. In addition, expression profiles with drug treatment were obtained using Illumina HumanHT-12 v4 Expression BeadChip and gene set enrichment analysis (GSEA) was performed with GSEA application. Orthotopic tumor model was generated and assessed for tumor margin. Results: The compound activated p-AMPK and reduced phosphorylation of mTORC-1-regulated proteins. It decreased stemness of gCSCs, proved by sphere formation assay and decreased expression of stemness markers. The invasive properties of gCSCs were inhibited on 3D invasion assay and the expression of proteins related with epithelial-mesenchymal transition was inhibited by the compound. GSEA revealed cell adhesion related gene set was altered in the compound treated groups. Orthotopic model of the tumor showed less invasive tumor margin on the treatment of the compound. Citation Format: Junjeong Choi, Ji-Hyun Lee, Jin-Kyoung Shim, Kim Pilnam, Seok-Gu Kang. Inhibiting stemness and invasion property of glioma stem cells by biguanide compound. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-26.