Research Paper Volume 12, Issue 22 pp 22949—22974

In vitro and in vivo efficacy of the novel oral proteasome inhibitor NNU546 in multiple myeloma

Figure 5. Effects of NNU546 and ixazomib on tumor growth in PDX model. (A) Relative tumor growth of PDX models treated orally with vehicle, ixazomib (5 mg/kg, BIW) or NNU546 (1 mg/kg, QD) scheduled for 3 weeks. Data were presented as mean ± SD (n=6;, p < 0.05). (B) Differences in tumor size for the vehicle and treatment groups. The tumors were resected from the NCG mice at the end of the experiment. (C) Average tumor weight in the vehicle and treatment groups. Data were shown as mean ± SD (, p < 0.05). (D) Left, H&E and immunostaining of tumor sections of vehicle, ixazomib and NNU546 treated mice, including apoptosis-associated TUNEL (green color), proliferation marker Ki-67 (red color) and angiogenesis markers CD31 (green color) and α-SMA (red color), detected using confocal microscopy (PerkinElmer UltraVIEW Vox, magnification, ×200 or ×400, nine continual fields put together). Right, the tissue sections were screened under a low-power field, and five fields were selected. Each field was analyzed separately to obtain the fraction of apoptotic cells, ki67 positive cells fluorescent areal density and microvessel density. The data is presented as mean ± SD per across the fields, (*, p < 0.05; **, p < 0.01; ***, p < 0.001). TUNEL, terminal deoxynucleotidyl transferase deoxyuridinetriphosphate nick end labelling; PDX, patient-derived xenograft; SMA, smooth muscle actin; SD, standard deviation.