XBP1 signaling impairs GCB DLBCL tumor growth. (A-D) Immunodeficient AGR129 mice were injected subcutaneously with 2.5 × 106 HBL1 (A-B) or 3 × 106 SUDHL4 cells (C-D) that express XBP1s under treatment with doxycycline. Mice were daily-administered vehicle or doxycycline at 1 mg/mL concentration through water as described in “Materials and methods.” Mean tumor volume measurements were represented against the days of treatment (A,C). P values were calculated using 2-way ANOVA followed by Bonferroni posttest; n.s., P > .05, *P ≤ .05, **P ≤ .01, ***P ≤ .001. Efficiency of doxycycline-induced XBP1s expression and its target genes was validated by immunoblot and quantitative real-time PCR for the mice carrying HBL1-XBP1s (B) or SUDHL4-XBP1s tumors. (D) Each dot in the graph represents relative gene expression for a single mouse (B and D bottom panels). P values were calculated using the unpaired Student t test to compare nontreated vs treated groups; ***P ≤ .001.
