Objective:To investigate the effects of histone deacetylase inhibitor trichostatin A (TSA), on the cell growth of human pancreatic cancer cell line PANC-1 in vitro and its mechanism.
Methods:The proliferating activity of PANC-1 cells was observed by MTT assay. The cell apoptosis and cell cycle distribution were detected by flow cytometry. Western blot and real-time PCR were used to assess the expression levels of inhibitor of apoptosis gene bcl-2 and cell cycle regulation gene p21 WAF1/CIP1.
Results:A dose dependent inhibition was remarkably confirmed in PANC-1 cells treated by TSA. As compared with control group, apoptosis rate of PANC-1 cells in TSA group was increased obviously at 72h (P＜0.05). The percentage of G 0/G 1 phase increased markedly, while the percentage of S phase decreased significantly (P＜0.05). Furthermore, the expression level of bcl-2 mRNA and protein in TSA group was significantly lower than that in control group (P＜0.05). The expression level of p21 WAF1/CIP1 mRNA and protein in TSA group was significantly higher than that in control group (P＜0.05).
Conclusions:Our data demonstrate that TSA-induced growth arrest of pancreatic cancer cell line is induced by a block in the G 0/G 1 phase and apoptosis, which may occur through down-regulated expression of apoptosis gene bcl-2 and up-regulated expression of cell cycle regulation gene p21 WAF1/CIP1.