Figure 5
c-Myc/NOXA pathway plays an important role in ixazomib induced proliferation inhibition in ESCC cells. (A) Kyse150 and Kyse 510 were treated with or without ixazomib 1μM for 48h, Cell lysate was prepared and c-Myc and NOXA protein level was determined by Western blotting analysis. (B, C) After transfected with the c-Myc siRNA for 48 h, Kyse150 and Kyse510 cells were further treated with ixazomib (1μmol) for 48 h and the cell viability and colony formation were examined. Values are the means ± SEM (n = 5-6). *P < 0.05 or **P < 0.01 indicates significant differences from the vehicle group as assessed by a two-tailed unpaired Student’s t test.
Figure 6
Isobologram analysis for the interaction of various combinations of ixazomib and chemotherapy agents on (A) Kyse150 and (B) Kyse 510 esophageal squamous cell lines.
Figure7
Ixazomib inhibits the growth of ESCC tumors in mice xenograft models. (A) The images of xenograft tumors at the end of the experiment. (B, C) Representative images of NOXA and c-Myc staining of ESCC-xenografted tumor sections in different treatment groups (200X magnification). (D) The organs including heart, spleen, liver and kidney from the mice treated with ixazomib 10 mg/kg were shown in the first row. The organs from the mice treated with vehicle control were shown in the second row. (E) Volume measurements of Kyse150 xenograft tumors treated with vehicle or ixazomib at the indicated dosages for 30 days. Ixazomib was administered by intragastric administration every other day at 10 mg/kg. (F) The body weight of mice in different treatment groups. Values are the means ± SEM (n = 6). *P < 0.05 or **P < 0.01 indicates significant differences from the vehicle group as assessed by a two-tailed unpaired Student’s t test.