Conclusions
Histone deacetylase inhibitors offer a potential novel epidrug approach for pancreatic cancer by reversing the undifferentiated phenotype and allowing patients to overcome resistance and better respond to conventional cytotoxic treatments.
Methods
PANC-1 (poorly differentiated) 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 blotting.
Results
Treatment of PANC-1 cells over 4 days with 0.5 μM TSA restored cellular differentiation, inhibited proliferation, and enhanced p21 protein expression. Trichostatin A upregulated NDRG1 mRNA and protein levels under normoxia from day 1 and by 6-fold by day 4 (P < 0.01 at all time points). After 24 hours 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. Conclusions: Histone deacetylase inhibitors offer a potential novel epidrug approach for pancreatic cancer by reversing the undifferentiated phenotype and allowing patients to overcome resistance and better respond to conventional cytotoxic treatments.