Fig. 1: CDC7 inhibitor-mediated aneuploid cells exhibit senescence phenotype. | Nature Communications

Fig. 1: CDC7 inhibitor-mediated aneuploid cells exhibit senescence phenotype.

From: CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade

Fig. 1

a Phase-contrast microscopy images of TAK-931-treated HeLa cells (scale bar = 100 μm). Representative images from n = 3 independent experiments with n = 5 technical replicates for each experiment are shown. b Representative histograms from cell cycle analysis of TAK-931-treated HeLa cells. c Side-scatter histograms of TAK-931-treated HeLa cells. d Representative images of SA-βGAL staining of cells after 72 h treatment (HeLa, A549: scale bar = 50 μm, COLO205: scale bar = 100 μm). Representative images from n = 3 independent experiments with n = 5 technical replicates for each experiment are shown. e Quantitative reverse transcription–PCR (qRT–PCR) analysis of SASP genes in TAK-931-treated HeLa cells after 72 h of treatment. Data are presented as mean ± SD (n = 3 independent experiments), Two sided Student’s t test p = 0.000, p = 0.001, and p = 0.001, respectively. f Representative histograms from cell cycle analysis of combination TAK-931 and VE-821 treatment. COLO205 cells were treated with DMSO (upper left), TAK-931 at 300 nM (upper right), VE-821 at 1000 nM (lower left), or the combination (lower right) for 24 h. g Representative images of SA-βGAL staining after combination treatment. COLO205 cells were treated with DMSO (upper left), TAK-931 at 300 nM (upper right), VE-821 at 1000 nM (lower left), or the combination (lower right) for 24 h (scale bar = 50 μm). Representative images from n = 3 independent experiments with n = 5 technical replicates for each experiment are shown. h qRT–PCR analysis of SASP genes after combination treatment. COLO205 cells were treated with TAK-931 alone (red) or TAK-931 + VE-821 (blue) at the indicated concentrations for 24 h. Data are presented as mean ± SD (n = 3 independent experiments). Two-sided Student’s t test p = 0.004 and p = 0.000, respectively. i IRF reporter activity in TAK-931 and BMS-265246 treatments. A549 reporter cells were treated with indicated drug treatments and subjected to IRF-Luc reporter assays. Data are presented as mean ± SD (n = 4 independent experiments). Two-sided Student’s t test p = 0.000. j qRT–PCR analysis of IL6 and CXCL10 after combination treatment. A549 reporter cells were treated with the indicated drug treatments. Data are presented as mean ± SD (n = 3 independent experiments). Two-sided Student’s t test p = 0.000 and p = 0.000, respectively. Source data are provided as a Source Data file.

Back to article page