Figure 4.

Overexpression of p53^R248Q in OVCAR3 cells increased sensitivity to gefitinib or JNJ. In this experiment, OVCAR3 cells were pre-transfected with either empty plasmid (1 μg/mL) or p53^R248Q (1 μg/mL) for 18 h and then exposed to the inhibitors alone or in combination for another 48 h. The doses of gefitinib and JNJ ranged from 5 to 40 μM and 1 to 36 μM, respectively. The concentrations of gefitinib and JNJ in combination were prepared in a one-to-one ratio, with doses ranging from 0.5 to 12 μM. The effects on cell proliferation were assessed by CCK-8 assay; the half maximal inhibitory concentration (IC₅₀) values (in log10) were calculated by GraphPad Prism 6. (A) In the absence or (B) in the presence of p53^R248Q overexpression, the combined treatment of gefitinib and JNJ significantly reduced the IC₅₀ values for each agent in OVCAR3 cells (*** p < 0.001 vs. gefitinib and JNJ). (C,D) The sensitivities to gefitinib or JNJ alone increased significantly in p53^R248Q-overexpressing cells (** p < 0.01; *** p < 0.001). (E) No significant difference was found when the combination treatment of gefitinib and JNJ was applied to the plasmid-only transfected cells and the p53^R248Q-overexpressing cells.