Figure 5.

Upregulation of SAMHD1 was associated with the resistance of poly(ADP‐ribose) polymerase inhibitors (PARPi)‐resistant variants to Ara‐C. A, Cells were treated with the indicated drugs for 72 hours and then subjected to sulforhodamine B (SRB) assays. IC ₅₀ values (left panel) were calculated from 3 independent experiments and expressed as mean ± SD. The resistance factor (right panel) is the ratio of the averaged IC ₅₀ value of the indicated drug in the given resistant cells to that of the same drug in the parental U251 cells. b, Levels of γ‐H2AX induced by Ara‐C reduced in the resistant cells determined by western blotting. C, mRNA level of SAMHD1 was detected by qRT‐PCR and normalized using that of the parental U251 cells. **P < .01; ***P < .001. D, Protein level (upper) and distribution (lower) of SAMHD1 detected by western blotting and immunofluorescence, respectively. Scale bar: 5 μm. E, CRISPR/Cas9‐mediated knockout of SAMHD1 in U251/OP cells was confirmed by western blotting. f,g, cells were treated with Ara‐C for 3 days (F) or PARPi for 7 days (G) and then subjected to SRB assays. Data from 3 independent experiments were expressed as mean ± SD