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May 22-23, 2019 | Rome, Italy
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
alliedacademies.comYEARS
IMMUNOLOGY
AND CANCER THERAPY
2
nd
Global Summit on
Immunotherapy 2019
Immunology Case Reports | Volume 3
HISTONE DEACETYLASE INHIBITION RESTORES EXPRESSION OF HYPOXIA-INDUCIBLE
PROTEIN NDRG1 IN PANCREATIC CANCER
Céline Tiffon
National Cancer Institute, France
P
ancreatic ductal adenocarcinoma affects both men and women and is highly aggressive, with a five-year
survival rate of only about 5%. N-Myc downstream regulated gene-1 (NDRG1) is a hypoxia-inducible and
differentiation-related protein and candidate biomarker in pancreatic cancer. As NDRG1 expression is lost in
high-grade tumors, the effects of the differentiating histone deacetylase inhibitor trichostatin A (TSA) were ex-
amined in human pancreatic cancer cell lines representing different tumor grades. Panc-1 (poorly differentiat-
ed) and Capan-1 (moderately- to well-differentiated) cells were treated with TSA. Effects were assessed
in vitro
by microscopic analysis, colorimetric assays, cell counts, real-time polymerase chain reaction and western blot-
ting. Treatment of Panc-1 cells over four days with 0.5 µM TSA restored cellular differentiation, inhibited prolif-
eration and enhanced p21Cip1 protein expression. Trichostatin A upregulates NDRG1 mRNA and protein levels
under normoxia from day one and by six-fold by day four (p<0.01 at all-time points). After 24hrs under hypoxia,
NDRG1 expression was further increased in differentiated cells (p<0.01). Favorable changes were identified in
the expression of other hypoxia-regulated genes. HDAC inhibitors offer a potential novel epi-drug approach for
pancreatic cancer by reversing the undifferentiated phenotype and allowing patients to overcome resistance
and better respond to conventional treatments. Restoration of NDRG1 expression may represent a biomarker
of malignant pancreatic tumors undergoing re-differentiation and redirecting toward a lower tumor grade. The
use of the human ductal Panc-1 cell line treated with TSA represents a useful tool to study cellular differentia-
tion through epigenetic mechanisms. Furthermore, lifestyle and environmental factors especially nutrition and
chemical exposure, induce effects on human health from gestation and beyond via epigenetic modifications.
Céline Tiffon, Immunol Case Rep 2019, Volume 3
Céline Tiffon obtained her PhD in Tumor Biology from the University of Bern, Switzerland and working on the subject of liver and
pancreatic cancers. She carried out Postdoctoral Research at the Cancer Science Division of the University of Southampton, United
Kingdom. Her research interests focused on the molecular mechanisms triggered by two licensed HDAC inhibitors in cutaneous
T-cell lymphoma with a particular emphasis on cytokine expression. She continued with Postdoctoral Research at the University of
Burgundy, France and working on the topic of endocrine disruptors. Currently, she is working as a Scientific Officer at the National
Cancer Institute, France.
celine.tiffon@gmail.comBIOGRAPHY