Fig. 6: PIN1 inhibitors synergize with CDK4 inhibitors against TNBC in human cells and immune-compromised mouse models.
From: Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry
Colony formation of MDA-MB-231 (a) and SUM-159 cells (b) treated with Sulfopin and Palbociclib for 2 weeks. c IB analysis of PIN1 in SUM-159 cells treated as in (b). d Correlation of cell growth inhibition (b) and PIN1 abundance (c) in SUM-159 cells. Two-sided p value for Pearson correlation coefficient. e Cell counts of MDA-MB-231 cells treated with 1 μM Palbociclib, 10 μM Sulfopin or their combination for 4 days. n = 3 independent experiments. Data in graphs are mean ± SD and analyzed by unpaired two-sided t-test. p values are shown. f MDA-MB-231 cells were treated with increasing concentrations of indicated drugs for 3 days, followed by analyzing apoptotic and necrotic cells by FACS. n = 2 independent experiments. g Tumor growth of TNBC PDOX from different treatments. Data in graphs are mean ± SEM and analyzed by unpaired two-sided t-test. Mice numbers and p values are shown. h Tumor sizes were shown when mice were euthanized after 45 days. NT, no tumor detectable. i Representative immunofluorescence images for PDOX tumors stained with PIN1 (green) and Ki67 (red). Scale bars, 50 µm. j Tumor growth of MDA-MB-468 xenografts from different treatments. k Tumor weights were measured when mice were euthanized after 7 weeks. n = 5 mice per group (j, k). Data in graphs are mean ± SEM and analyzed by unpaired two-sided t-test. p values are shown (j, k). l Representative immunofluorescence images for MDA-MB-468 xenografts tumors stained with PIN1 (green), Ki67 (red) and Geminin (pink). Scale bars, 50 µm. m Growth curves (left) and tumor weights (right) of K14cre; Brca1wt/f; p53wt/f_BT3 tumors from different treatments, n = 6 mice per group. n Growth curves (left) and tumor weights (right) of K14cre; Brca1wt/f; p53wt/f_BT1 tumors from different treatments, n = 5 mice per group. Data in graphs are mean ± SEM and analyzed by unpaired two-sided t-test (m, n). p values are shown (m, n). The images were representative images from 3 independent experiments (a–c). Source data are provided as a Source Data file.
