RSL3 and BTZ synergistically inhibit t(4;14)-positive tumor growth in vivo. (A) Schematic diagram of the xenograft model. NCI-H929 cells were injected subcutaneously into NOD SCID mice to establish a xenograft model. When tumor (vol.) reached ∼50 to 80 mm3, the mice were randomized to receive eith solvent control (vehicle), BTZ (0.5 mg/kg, biweekly), RSL3 (5 mg/kg, every 2 days), or BTZ plus RSL3 treatment IP for 3 weeks (n = 5). (B) Growth curves of the xenograft tumors. Tumor volumes of each group were assessed every 3 days. (C) Weights of xenograft tumors. Tumor weights of each group were evaluated on the day of mice euthanasia. The CDI was calculated to test for synergy using mean tumor weight measurements. The CDI value of 0.55 indicates synergy (defined as CDI < 1, with CDI < 0.7 indicating a significant synergistic effect). (D) Immunohistochemical analysis of ki-67, cleaved-caspase3, and 4-HNE protein levels in tumor tissues from NCI-H929-xenografted mice treated with solvent control (Ctrl), BTZ, RSL3, or BTZ plus RSL3. Scale bar: 100 μm. (E) Expression levels of targeted proteins in mice of treatment groups were quantitatively analyzed using Image J. ∗ P <0 .05, ∗∗ P < .01, and ∗∗∗ P < .001.
