Abstract:
Objective This work aimed to investigate the effects of LBH589, a novel histone deacetylase (HDAC) inhibitor, alone or in combination with docetaxel (DTX) on the proliferation and apoptosis of the human ovarian cancer cell line OVCAR-3.
Methods OVCAR-3 cells were treated with LBH589, DTX, or a combination of both at various concentrations. The proliferation capacity, apoptosis rate, and reversal of drug resistance were evaluated by MTT assay. The apoptotic rate of the cells was detected using trypan blue and acridine orange/ethidium bromide double-staining methods. The expression of proteins such as poly-ADP-ribose polymerase (PARP), caspase-3, caspase-7, bel-2, and bax were analyzed by Western blot analysis.
Results Synergistic cytotoxicity was observed in the combination therapy using low doses of LBH589 and DTX against OVCAR-3 cells. The synergistic effect was confirmed by Calcusyn software analysis. OVCAR-3 cells apparently increased in number in the combination therapy than in either LBH589 or DTX therapy alone. Western blot analysis showed that the expression of cleaved PARP-85KD, caspase-3, and bax increased, whereas bcl-2 was downregulated.
Conclusion LBH589 and DTX in vitro can significantly inhibit the proliferation of human ovarian cancer cell line OVCAR-3 and induce cell apoptosis of these cells. Combined LBH589 and DTX treatment against drug-resistant OVCAR-3 cells resulted in a synergistic effect of increased sensitivity to chemotherapy.
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