Page 110 - 2019_12-Haematologica-web

M. Wu et al.
WEE1inhibitorMK1775andRAD51inhibitorB02(Figure 4A). Furthermore, synergistic effects between these DDR inhibitors and ara-C were observed at markedly lower
Flow cytometric analysis of cellular gH2AX levels revealed that increased DNA damage (% high γH2AX) was significantly more frequent in DOCK2 KD MV4;11 cells than in control MV4;11 cells after treatment with ara- C (2 μM), alone or in combination with MK8776 (0.1 μM),
concentrations in DOCK2 KD MV4;11 Supplementary Figure S4C).
A
cells
(Online
B
Figure 4. Suppression of DOCK2 expression rendered MV4;11 cells more sensitive to MK8776, MK1775 and B02. (A) Compared to control cells, DOCK2 knokcdown (KD) MV4;11 cells exhibited increased percentages of apoptotic cells upon treatment with MK8776, MK1775 and B02, both alone and in the presence of ara-C. Cells were treated for 48 h. The assays were performed in triplicate. (B) Compared to control cells, a higher percentage of DOCK2 KD MV4;11 cells harbored elevated DNA damage (as indicated by an elevated gH2AX signal) upon treatment with ara-C (2 μM), as well as with MK8776 (0.1 μM), MK1775 (0.1 μM), and B02 (20 μM), both alone and in combination with ara-C. Treatment with MK8776, MK1775 and B02 in combination with ara-C resulted in an increased mean gH2AX signal in DOCK2 KD MV4;11 cells compared to cells treated with ara-C alone. Cells were treated for 16 h. *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. C: cells expressing con- trol short hairpin (sh)RNA; KD: cells expressing an shRNA against DOCK2.
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haematologica | 2019; 104(12)