Extended Data Fig. 8: Preclinical scheme, tumor assessment and SASP analysis.
a, Schematic illustration of drug administration and tumor surveillance. Cancer cells (PC3) alone or alongside stromal cells (PSC27) were inoculated subcutaneously to NOC/SCID mice 2 weeks prior to chemotherapy. MIT was provided on the 1st day of each week starting from the 3rd week, then given every other week with a total number of 3 doses. b, Statistics of tumor end volumes. PC3 cells were xenografted to animal hind flank. MIT was administered to induce tumor regression, alone or together with ML324. c, Growth curves of tumors grown in PC3 mice subjected to indicated treatments. Measurements started from the 14th day after tumor xenografting until end of the regimen. d, Growth curves of tumors grown in PC3/PSC27 mice subjected to indicated treatments. Measurement period was the same as described in (c). e, Statistical profiling of tumor end volumes. PC3 cells were xenografted alone or alongside with PSC27 cells (pre-transduced with scramble or KDM4A/B-specific shRNAs via lentivirus) to the hind flank of NOD/SCID mice. Chemotherapeutic agent MIT was used to treat animals. Constructs encoding shRNAs were transduced to cancer or stromal cells in experiments depicted on the left and right parts as indicated, respectively. f, Quantitative transcript analysis of E-cadherin and vimentin, cell lineage-specific markers for epithelial and stromal cells, respectively. g, Transcript analysis of canonical SASP factors expressed in epithelial and stromal cells, respectively. Individual cell types were isolated from tumor tissues via LCM. Expression of p16INK4a and p21CIP1 was measured to determine in vivo cellular senescence. Data shown as mean ± SD and representative of 3 independent experiments. c,d, P values were determined by two-way ANOVA, and adjusted for multiple comparisons. e, P values were determined by one-way ANOVA, and adjusted for multiple comparisons. b, f–g, P values were determined by two-sided unpaired t-test, and adjusted for multiple comparisons. f–g, median, 25th and 75th percentiles, with Turkey whispers indicated in box-and-whisker plots and extending to values no further than 1.5 × IQR from either upper or lower hinge.
