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Page 27 of 36 J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21

opposite fashion the expression of BMI-1, a Polycomb transcriptional repressor belonging to the Hedgehog
pathway, involved in cancer cell stemness and metastasis. Interestingly, BMI-1 silencing restores autophagy
and halts ovarian cancer cell migration. Our data indicate that there is a functional cross-talk between
autophagy and Hedgehog/EMT/cell migration processes and we propose BMI-1 as the joining mediator.

In conclusion, our findings indicate that RV elicits its anti-tumor effect through induction of autophagy and
down-regulation of BMI-1, and that this process is sufficient to inhibit cancer cell migration and invasion.

34. Effects of HDAC inhibitors on glioblastoma cells

4
3
1,2
5,6
Olga Pastorino , Maria Teresa Gentile , Adriana Bajetto , Antonella Di Costanzo , Alessandro Mancini ,
1
3
4
Lucia Altucci , Tullio Florio , Maria Patrizia Stoppelli , Luca Colucci D’Amato 1
2
1 Laboratory of Molecular and Cellular NeuroPathology, Di.S.T.A.Bi.F., University of Campania “L.
Vanvitelli”, Caserta 81100, Italy.
2 Istituto di Genetica e Biofisica “ABT”, CNR, Naples 80131, Italy.
3 Sezione di Farmacologia, Dipartimento di Medicina Interna & Centro di Eccellenza per la Ricerca
Biomedica (CEBR), Università di Genova, Genova 16132, Italy.
4 Dipartimento di Medicina di Precisione, University of Campania “L. Vanvitelli”, Caserta 81100, Italy.
5 Dipartimento di Scienze Mediche Traslazionali, University of Campania “L. Vanvitelli”, Caserta 81100, Italy.
6 BIOUP Sagl, Lugano 6900, Switzerland.

Background: Glioblastoma Multiforme (GBM), a high-grade glioma (WHO grade IV), is the most
aggressive form of brain cancer. Treatment options for GBM involving a combination of surgery,
chemotherapy and radiation resulted in a poor survival outcome. Epigenetic mechanisms are increasingly
implicated in GBM pathogenesis. Unlike genetic mutations, epigenetic changes arereversible and can be
targeted by drugs. We evaluated whether different histone deacetylase Inhibitors (HDACis) are able to
affect migration, invasion and vasculogenic mimicry in GBM cells.

Methods: We tested Varinostat (SAHA) and Trichostatin A (TSA) as inhibitors of class I and II HDACs,
Entinostat (MS275) as selective inhibitor of class I HDACs (specifically of HDAC 1 and 3) and MC1568 as
selective HDAC class II inhibitor. Tube Assay was used to evaluate the ability of HDAC is to interfere with
vessels formation by human GBM U87MG and rat glioma C6 cell lines and by cancer stem cells (CSCs)
isolated from human GBMs. U87MG directional cell migration and cell invasion have been assessed by
Boyden chamber assay and using xCELLigence Real-Time Cell Analyzer. Trypan Blue exclusion test and
MTT assay were employed to assess cell viability and cell proliferation.

Results: Our data show that sublethal doses of HDACis significantly decrease U87MG directional cell
migration and that MS275 HDACi is able to impair U87MG matrigel invasion. Finally, we observed that
HDACis inhibit significantly vasculogenic mimicry in U87MG, C6 and CSCs cells.

Conclusion: GBM depends on vascular networks to supply blood, oxygen, and nutrients. Tumor blood
vessels can either be formed from pre-existing blood vessels (neo-angiogenesis) or from tumor cells
(vasculogenic mimicry) due to a process of epithelial-mesenchymal transition; vascular mimicry provides
a mechanism whereby GBM could escape anti-angiogenic therapies. Our results suggest that HDACis may
be promising candidates for blocking vascular mimicry.