Abstract 2534: Low glucose and hypoxia environment promote the enrichment of liver cancer stem cells

Cancer stem cells (CSCs), a subpopulation possess tumor initiation and self-renewal capacity, are responsible for recurrence, metastases and drug resistance. Thus, it is important to understand their biology for identification of new therapeutic approaches. Liver surgery and/or transarterial (chemo) embolization (TAE/TACE) therapy usually generate a microenvironment that fosters aggressive tumor recurrence. These areas are characterized by chronic hypoxia and possibly low glucose concentration. Here, we tested the hypothesis that whether hypoxia along with low glucose environment promote the expansion of CSC population in HCC cells. We cultured human liver cancer cell line-Huh7 cells in normoxia or hypoxia condition with high or low glucose medium. The EMT markers (N-cadherin and Vimentin) but not stemness genes (CD44 and CD133) were upregulated in hypoxia condition. However, all genes were significantly induced under low glucose/hypoxia condition. In addition, results from sphere assay showed that low glucose/hypoxia condition dramatically improved the sphere formation ability of Huh7 cells, while low glucose or hypoxia along cannot promote sphere formation. Moreover, Huh7 cells cultured in low glucose/hypoxia condition displayed a lower sensitivity to cisplatin and doxorubicin treatment compared to cells maintained in high glucose/normoxia condition. Therefore, our findings suggested that low glucose concentration and hypoxia environment remarkably promote the enrichment of liver CSCs which could be useful for developing novel therapeutic modalities. Citation Format: Chih Chung Lai, Tsu-Hsiang Shia, Yu-Peng Liu, Chia-Hung Yen. Low glucose and hypoxia environment promote the enrichment of liver cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2534.