Fig. 4: In vitro and in vivo efficacy of CFI-400945 in combination with doxorubicin in DLBCL.

a Reductions in cell viability induced by CFI-400945, doxorubicin and CFI-400945 and doxorubicin combination in LY8 and LY3 cells after incubation of 48 h. b Apoptosis induced by CFI-400945, doxorubicin, and CFI-400945 plus doxorubicin after 48 h in LY8 and LY3 cells. Data are shown as the mean ± SD, n = 3. *P < 0.05, ****P < 0.0001 c A schema for showing the experimental design of the mice experiment. LY8 cells were injected subcutaneously into SCID/Beige mice. Seven days after injection, mice were treated with CFI-400945 monotherapy, doxorubicin monotherapy or the combination treatment. Doxorubicin was administered on day 1, intravenously, while CFI-400945 was dosed orally and daily for 21 days. Bioluminescent signals were taken at the indicated time points. n = 6 for each group. d Representative image of tumor growth curves. Data are shown as the mean ± SD, n = 6. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 e Bioluminescence images of mice from different groups. f Representative images of immunohistochemical staining for γ-H2AX and Ki-67 in DLBCL xenograft tumors. Scale bar: 50 μm. g Analysis of mitotic status by HE staining to illustrate cells with aberrant mitosis (arrow) in DLBCL xenograft tumors after the combination treatment. Scale bar: 10 μm.