Extended Data Fig. 7: Schematic design of preclinical trial and comparative gene expression analysis.
From: PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy
a. Statistics of tumor volumes in mice carrying cancer cells (PC3) and stromal cells (PSC27) as indicated. Tumor volumes measured at end of an 8-week period. b. Statistics of tumor volumes before animal exposure to chemotherapeutic agent mitoxantrone for senescence induction. c. Experimental workflow. Human cells inoculated subcutaneously to NOD/SCID males 2 weeks before chemotherapy. Agents delivered on 1 st day of each week starting from 3 rd week, then given every other week, totally 3 doses. Animals sacrificed 8 weeks later, tumors measured and tissues assessed. d. Transcript expression profiling of indicated factors. Individual cell types isolated from tumor tissues via LCM. Data representative of 3 biological replicates (n = 10 animals per group). e. Statistics of tumor volumes. LNCaP cells xenografted together with PSC27 to the hind flank, with MIT and/or PDK4 inhibitor PDK4-IN delivered via intravenous injection in a manner resembling PC3/PSC27 regimen. f. Statistics of tumor volumes. 22Rv1 cells were xenografted together with PSC27 to the hind flank, with MIT and/or PDK4-IN delivered via intravenous injection in a manner resembling PC3/PSC27 regimen. g. Statistics of tumor volumes. MDA-MB-231 (MDA) cells were xenografted together with HBF1203 to the hind flank, with DOX and/or PDK4-IN delivered via intravenous injection in a manner resembling PC3/PSC27 regimen. h. Statistics of circulating lactate concentration in serum. Peripheral blood of mice subject to lactate measurement at the end of regimen. PC3 and/or PSC27 cells were exposed to MIT in culture for senescence induction before implantation. Data in a, b, d-h are shown as mean ± S.D. and represent 3 biological replicates. For box and whiskers graphs (d), the minima, maxima, median, 25th and 75th percentiles are shown, with whiskers indicating smallest and largest values. For each dataset, n = 10 per treatment arm. P values were calculated by two-sided unpaired Student’s t-tests (a-b, d-h) or one-way ANOVA (a-b). MIT, mitoxantrone. DOX, doxorubicin. ^, P > 0.05. *, P < 0.05. **, P < 0.01. ***, P < 0.001. ****, P < 0.0001.
