Fig. 7

Enzastaurin and ibrutinib have synergistic antitumor effects in a DLBCL models in vivo. NPG mice subcutaneously inoculated with HBL-1 (5 × 10⁶) cells were randomized in four groups, respectively, treated as follow: enzastaurin (orally, 125 mg/kg, BID), ibtutinib (orally, 12 mg/kg, BID), combination of enzastaurin plus ibtutinib and control vehicle (n = 8 per group). a Tumor size curves derived from HBL-1 xenograft mouse model. b Body weight curves derived from HBL-1 xenograft mouse model. c-d Apoptosis of tumor tissue was assessed by the TUNEL assay; the nuclei were counterstained with DAPI. Representative images show apoptotic/fragmented DNA (green staining) and the corresponding cell nuclei (blue) staining. Scale bar 10 μM. Results are expressed as mean ± SEM. e-f Immunohistochemistry assay of Ki-67, p-BTK and p-PKCβ protein expression in xenograft tumors. e Representative pictures of immunohistochemistry staining in sections are shown (Scale bar 60 μM). f The data represents the density of positivity cells for each section. Values are expressed as percentages of vehicle in mean ± SD, * p < 0.05 compared with vehicle group, ** p < 0.01 compared with vehicle group, *** p < 0.001 compared with control group; # p < 0.05 compared with enzastaurin group, ## p < 0.01 compared with enzastaurin group