Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

1646 - Hypoxia, Inflammation and redox status as determinants of malignant progression of cancer stem cells


10 Sep 2017


Poster display session


Translational Research;  Central Nervous System Malignancies


Marco Papale


Annals of Oncology (2017) 28 (suppl_5): v109-v121. 10.1093/annonc/mdx366


M. Papale

Author affiliations

  • Medicina Sperimentale, Sapienza – Università di Roma, 185 - Roma/IT


Abstract 1646


Transformed cells live in a hostile environment characterized by lack of oxygen. Hypoxia produces: necrosis with alarmins release; activation of HIF1a. Recent studies have shown that HIF1a controls also the expression of membrane receptors in tumor cells. These receptors are part of the inflammatory reparative response (IRR) and have the capacity to bind and be activated by alarmins. Once activated, their signaling cascades lead to NFkB. Human tumor tissues posses 1-2% of cancer stem cells (CSCs) responsible for the metastatic potential of tumors. In particular, we investigated the overall hypothesis that, in CSCs from a primary tumor, hypoxia links the expression of IRR genes to tumor progression.


Hypoxia was achieved in a hypoxic chamber, where a 1% oxygen mix was flushed in for 4 min. Hypoxic response as well as efficacy of drugs treatments on CSCs was determined by measuring HIF1a, VEGF and other markers by WB and Immunofluorescence. Inflammation-like status was reproduced by treatment with necrotic extracts. Redox status was determined by the DCFH-DA. Expression of IRR and adhesion genes was determined by RT-PCR.


Initially, two cell lines of Glioblastoma CSCs from two different tumors were selected and the protein and gene expression were analyzed by WB and RT-PCR. WB analysis showed that hypoxia promotes the expression of HIF1a and change the expression of other proteins directly related to HIF1a. Moreover the gene expression by RT-PCR showed many differences among the analyzed markers. Then we used multiple concentrations of digoxin and acriflavine in the two selected cell lines and also necrotic extracts. Both the drugs promote the reduction of the expression of HIF1a and other related markers. Moreover we used the drugs and an invasion assay kit for evaluation of invasive tumor cells. Also in this case, we observed modification in the invasiveness of CSCs.


Hypoxia promotes cells adaptation trough the expression of HIF1a, without new genetic mutations, and modify other HIF-target proteins such as VEGF, HKII, Rage. Using different concentrations of digoxin and acriflavine it is possible to modify protein and gene expression of HIF1a and related markers, modifing the production of ROS and the invasiveness of CSCs.

Clinical trial identification

Legal entity responsible for the study

Casa di cura San Raffaele Pisana - Rome


Ministero della salute


All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.