Effects of histone deacetylase inhibitor trichostatin A combined with cisplatin on apoptosis of A549 cell line

BACKGROUND: Histone deacetylase (HDAC) inhibitors combined with other drugs for the treatment of malignant tumors are used more and more widely. In this study, we investigated the effect of trichostatin A (TSA), a HDAC inhibitor, in combination with cisplatin, a cytotoxic chemotherapy agent, on the apoptosis of lung cancer A549 cells. METHODS: A549 cells were treated with TSA alone, cisplatin alone or the two drugs combined. Cell viability and apoptosis were evaluated using a light microscope, methyl thiazolyl tetrazolium (MTT) (3-[4, 5-dimethylthiazol-2-yl] −2, 5-diphenyltetrazolium bromide) assay and Hochst33258 staining. Moreover, Western blot analysis was employed to examine the alterations of apoptosis protein: cellular Fas-associated death domain-like interleukin-1 β converting enzyme inhibitory protein (cFLIP) and caspase-8 in A549 cells in response to the different exogenous stimuli. RESULTS: Compared with single-agent treatment, the co-treatment of A549 cells with TSA and cisplatin synergistically inhibited cell proliferation, induced apoptosis, and increased the inhibition rate. Treatment with TSA and cisplatin led to a significant decrease of cFLIP expression. Furthermore, the treatment of A549 cells with TSA and cisplatin resulted in a significant decrease of pro-caspase-8 and a significant increase of caspase-8. CONCLUSIONS: Synergistic anti-tumor effects are observed between cisplatin and TSA in lung cancer cells. The combination of TSA with cisplatin may be a more effective method in human lung cancer treatment.