N-myc downstream-regulated gene-1 (NDRG1), a hypoxia-inducible and differentiation-related protein, is a potential biomarker in pancreatic cancer. Because NDRG1 expression is reduced in high-grade tumors, the effects of the differentiating histone deacetylase inhibitor trichostatin A (TSA) in human pancreatic cancer cell lines representing different tumor stages were investigated. Cancer is a genetic disease caused by inherited or sporadic mutations in genes involved in tissue homeostasis, cell cycle control, and apoptosis. TSA was applied to PANC-1 (poorly differentiated) and Capan-1 (moderately to well differentiated) cells. In vitro evaluations included microscopic examinations, colorimetric assays, cell counts, real-time polymerase chain reaction, and Western blotting. PANC-1 cells were treated for four days with 0.5 M TSA. Cell differentiation was restored, proliferation was inhibited, and p21Cip1 protein expression was increased. Trichostatin A increased NDRG1 mRNA and protein levels in normoxia starting on day 1 and increasing by 6-fold by day 4 (P 0.01 at all time points). NDRG1 expression was increased in differentiated cells after 24 hours of hypoxia (P 0.01). Other hypoxia-regulated genes showed an increase in expression.
Conclusions: Histone deacetylase inhibitors have the potential to be a novel epidrug for pancreatic cancer, as they reverse the undifferentiated phenotype, helping patients to overcome resistance and respond better to traditional cytotoxic treatments.
Author (S) Details
Céline Tiffon
Independent Researcher, 50 rue des vignes 92000 Nanterre, Hauts-de-Seine, France.
View Book :- https://stm.bookpi.org/HMMR-V14/article/view/1647
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