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.
Department of Respiratory Healthcare Medicine, Shandong Provincial Hospital Affiliated to Shandong University Jinan, China.
Xuan
X
Zhang
Department of Respiratory (or Pulmonary) Medicine, Shandong Provincial Hospital Affiliated to Shandong University Jinan, China.
Shu-Juan
SJ
Jiang
Department of Thoracic Surgery Medicine, Shandong Provincial Hospital Affiliated to Shandong University Jinan, China.
Bin
B
Shang
Department of Respiratory Healthcare Medicine, Shandong Provincial Hospital Affiliated to Shandong University Jinan, China.
Hong-Juan
HJ
Jiang
Caspase-8; Trichostatin A (TSA); cellular Fas-associated death domain-like interleulin-1 β converting enzyme inhibitory protein (cFLIP); cisplatin