Panobinostat Synergistically Enhances the Cytotoxic Effects of Cisplatin, Doxorubicin or Etoposide on High-Risk Neuroblastoma Cells
Figure 3
Synergistic antitumor interactions between panobinostat and doxorubicin in SK-N-BE(2) cells.
Panels A, C, and E: The SK-N-BE(2) cells were treated with variable concentrations of panobinostat and doxorubicin with three different administration schedules including simultaneous treatment with the two drugs for 48 h (designated PAN+DOX, panel A), pretreatment with panobinostat for 24 h followed by simultaneous treatment with the two drugs for 24 h (designated PAN→DOX, panel C), and pretreatment with doxorubicin for 24 h followed simultaneous treatment with the two drugs for 24 h (designated DOX→PAN, panel E). Viable cells were measured by MTT assays and the data are presented as means ± standard errors from at least three independent experiments. Panels B, D, and F: Standard isobologram analyses of antitumor interactions between panobinostat and doxorubicin were performed in the SK-N-BE(2) cells treated under the three different administration schedules described above. The IC50 values of each drug are plotted on the axes; the solid line represents additive effect, while the points represent the concentrations of each drug resulting in 50% inhibition of growth. Points falling below the line indicate synergism, whereas those above the line indicate antagonism. PAN, panobinostat; DOX, doxorubicin. The same abbreviations were used throughout the study unless otherwise stated.