Fig. 4
CDK2/EZH2 blockade creates combination regimen with tamoxifen against TNBC. a Effective inhibition of TBNCs in 3D cultures by combination treatment of CDK2/EZH2 inhibitors (EPZ, GSK; SNS, and DINA) and TAM determined by 3D-Matrigel sphere formation assays. Representative images (upper panel) and bar graph of sphere numbers (bottom panel). Scale bar, 200 μm. b, c Synergistic effect of combination treatment of the TNBCs in vitro with CDK2/EZH2 inhibitors and TAM b or fulvestrant, Ful c. d, e Inhibitory effect of the combination therapy of CDK2 or EZH2 inhibitor and tamoxifen (TAM) on tumor growth in syngeneic mouse model. 4T1 cells were orthotopically transplanted on Balb/C female mice. The tumor-bearing mice were first pretreated with either EZH2i (EPZ-6438; EPZ) at 34 mg kg−1 or CDK2i (dinaciclib) at 8 mg kg−1 daily for 3 days, followed by combined with 4 mg kg−1 TAM for more than 2 weeks. The tumor burdens were measured with digital caliper (n = 10). *not significant, **p < 0.05, ***p < 0.01, ****p < 0.001, Student’s t test. f, g The effects of EZH2 (f) or CDK2 (g) inhibitor alone or in combination with TAM on TNBC tumor growth in a xenograft mouse model. TNBC SUM-149 cells were orthotopically inoculated on nude mice. The tumor-bearing mice were treated and monitored as described above d, e. EZH2i (GSK343) and CDK2i (dinaciclib) were administered at a dose of 100 mg kg-1 and 8 mg kg−1, respectively (n = 10). *not significant; ***p < 0.01; ****p < 0.001, Student’s t test. h Survival curves of tumor-bearing mice treated with CDK2i, TAM, or their combination (n = 10). *not significant, **p < 0.05, ****p < 0.001, Log-rank test. Source data are provided as a Source Data file.
