Fig. 6

Interrupting the "YB-1-PARP1" loop enhanced the tumor-killing effects of CDK4/6i. A. MDA-MB-231 cells were used to explore the effects of combined therapy in the nude mouse model. The mice were randomly divided into vehicle, abemaciclib, olaparib and combined groups when the tumor size reached 150 mm³. At least 6 nude mice were included in each group, and the nude mice were injected by intragastric administration 3 times a week with 100 mg/kg. The combined therapy of abemaciclib and olaparib synergistically suppressed tumor growth in the xenograft model. B–C. Tumor shape and size are shown for the 4 groups, and a ruler was used to determine the tumor volume. A comparison of tumor volume between groups is shown. D. The YB-1 inhibitor LJI308 combined with abemaciclib exerted a synergistic antitumor effect in MCF7AR cells, causing the xenograft tumor to shrink rapidly. E–F. Tumor shape and size are shown for the 4 groups, and a ruler was used to determine the tumor volume. A comparison of tumor volume between groups is shown. G. The sample derived from the animal tumor tissue was used to detect c-c3 (cleaved-caspase3), Ki67, and PARP1 expression in 4 groups. H. The IHC results of c-c3, Ki67, PARP1 and p-YB-1 are displayed for the effects on PARP1 expression induced by YB-1 inhibition. I–J YB-1 knockdown slowed the rate of tumor growth under abemaciclib treatment, and changes in tumor volume and tumor size are shown. The results presented have been repeated in 3 biological replicates. Data, means ± SEMs, *, P < 0.05, **, P < 0.01, ***, P < 0.001