Combination therapy of roniciclib and sorafenib in well-differentiated
thyroid cancer cells. (A) Cytotoxicity was evaluated in BHP7–13, K1,
WRO82–1 and FTC-133 cells treated with a series of six two-fold dilutions
of sorafenib starting at 10 μmol/L. Dose-response curves were obtained on
day 4 using LDH assays. (B) The median-effect dose (IC50) of sorafenib on day 4
was calculated for each cell line using CompuSyn software. (C) The cytotoxic
effects of roniciclib and sorafenib alone and in combination after a 4-day
treatment in BHP7–13, K1, WRO82–1 and FTC-133 cells were evaluated
using LDH assays. (D) The combination index (CI) of roniciclib and sorafenib was
calculated using CompuSyn software. The combination therapy of roniciclib and
sorafenib had synergistic effects in WRO82–1 and FTC-133 cells,
synergistic to additive effects in BHP7–13 cells and synergistic to
antagonistic effects in K1 cells. Synergistic effects appeared when the affected
fractions of BHP7–13 and K1 cells was lower (affected fraction <
0.9 and < 0.7, respectively). The horizontal line at CI = 1 was drawn for
discrimination of synergism (CI < 1) and antagonism (CI > 1).