Conclusions
HDACs inhibition could up-regulate placental P-gp expression in trophoblast cells, and HDAC1/2 was most likely to be involved in this process.
Methods
Human placental trophoblast cell lines (Bewo and JAR) were treated with two different HDAC inhibitors-suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) at different concentration gradients of 0.5, 1.0, 3.0 and 5.0 μM. Cells were harvested after 24, 48, and 72 h treatment. Total HDAC activity was detected by colorimetric assay Kits. HDAC1/2/3/ABCB1 mRNA and protein expressions were determined by real-time quantitative PCR and western-blot, respectively. Pearson correlation analysis test was performed to explore the relationship between HDAC1/2/3 mRNA and ABCB1 mRNA expression.
Results
SAHA and TSA could inhibit total HDAC activity and placental HDAC1/2/3 expression both in Bewo and JAR, but displayed a transient induction of HDAC mRNA or protein level after being treated at low dosage or prolonged exposure to drugs. Discordance in HDAC mRNA and protein expression was also observed. Placental P-gp expression was significantly induced in company with HDACs inhibition. There was a significant negative linear relationship between HDAC1/2 mRNA and ABCB1 mRNA expression. Conclusions: HDACs inhibition could up-regulate placental P-gp expression in trophoblast cells, and HDAC1/2 was most likely to be involved in this process.