Targeting OXPHOS with IM156 restores the sensitivity of the resistant cells to ibrutinib treatment. (A) Synergistic assay in the indicated cell lines and samples from patients with MCL. Synergistic scores were calculated by SynergyFinder 2.0. A score >0 (pink) indicated a synergistic effect of the 2 drugs. (B) Schematic illustration of PDXs of MCL and the treatment procedure. (C) PDXs of MCL. Freshly collected MCL-7 cells were inoculated subcutaneously into NSG mice, and tumor signals were monitored by the Xenogen IVIS Imaging System (Caliper Life) until they reached ∼1 × 108 radiance ps−1 cm2 sr−1, then treated with 25 mg/kg ibrutinib (intraperitoneally) at 5 days a week, 30 mg/kg IM156 (intraperitoneally) every other day for 3 weeks, or with a combination of the 2 drugs. Bioluminescence images of mice before and after treatment (left) and tumor growth curves (right) are shown. The color scale depicts the photon flux (photons per second) emitted by tumors. Error bars represent mean ± SEM (two-way ANOVA, ∗P < .05; ∗∗∗P < .001). (D) Shown are photographs of tumors (left) and tumor volumes (right) from each group on day 21 (∗P < .05; ∗∗P < .01). (E) No significant mouse body weight changes were observed during treatment.
