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Figure 4 | Cancer Cell International

Figure 4

From: Unique functions of CHK1 and WEE1 underlie synergistic anti-tumor activity upon pharmacologic inhibition

Figure 4

Combined WEE1 and CHK1 inhibition at anti-proliferative concentrations leads to synergistic induction of DNA damage. A, Concentrations of MK-1775 and MK-8776 were selected that alone have minimal effects on cell viability but in combination lead to inhibition of cell proliferation. Concentrations used in each cell line were, for A2058: 125 nM MK-1775, 150 nM MK-8776; for HT-29: 125 nM MK-1775, 300 nM MK-8776; and for LoVo: 40 nM MK-1775, 75 nM MK-8776. Top panel, Cells were treated with DMSO, MK-1775, MK-8776, or both compounds and viability for A2058, LoVo, and HT-29 cells was determined at 48 and 72 hours. Viability is shown as percentage of DMSO treated control cells. Middle panel, Cells were treated as above and collected at 24 and 48 hours following drug addition. To assess DNA damage, the percentage of γH2AX positive cells was determined by flow cytometry. Lower panel, Cells were treated as above and collected at 24 and 48 hours for mitotic index analysis, calculated by determining the percentage pHH3 positive cells by flow cytometry. B, KPL-1, NCI-H460, and T47D cell lines were treated with DMSO, 150 nM MK-1775, 300 nM MK-8776, or the combination of the two drugs and analyzed for viability, DNA damage, and mitotic index as described in (A).

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