Combination of Proteasome and Histone Deacetylase Inhibitors Overcomes the Impact of Gain-of-Function p53 Mutations

Figure 2

Gynecologic cancer cells with GOF TP53 are highly sensitive to proteasome inhibitors alone or in combination with LBH589/panobinostat. Sensitivity (as measured by percent viability relative to untreated control) to bortezomib (a, b) or MLN2238/ixazomib (c, d) alone or in combination with LBH589/panobinostat was examined in KLE endometrial cancer cells with R175H GOF mutant (a, c) and OVCAR3 ovarian cancer cells with R248Q GOF mutant (b, d). The concentration of LBH589/panobinostat used in (a–d) was based on sensitivity to LBH589/panobinostat alone in KLE (e) and OVCAR3 (f) cells. All experiments were performed three times. ; by two-way ANOVA with Sidak’s multiple comparison test.

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