Ixazomib inhibits the growth of ESCC tumors in mice
xenograft models
Based on the results of in vitro studies, we hypothesized that ixazomib
might have an anti-tumor effect in vivo. To address this hypothesis,
ESCC tumor xenografts were established in nude mice. Figure 7A shows
that ixazomib had a strong inhibition on the growth of human ESCC
xenografts. At the final measurement, the volumes of tumors from the
mice treated with Ixazomib dose of 10 mg/kg every other day was 745
mm3, while the size of the tumors in control mice has
already reached 1340 mm3. The tumor growth was
inhibited by 44.4% after treatment with ixazomib (Figure 7F). Then the
tumor specimens from mouse xenografts were subjected to
immunohistochemical staining for NOXA and c-Myc expression. The results
show that elevated NOXA expression was accompanied by an increase in
c-Myc expression level in the tumor tissue of ixazomib-treated group in
comparison with vehicle-treated control (Figure 7B, C). In order to
observe the delayed organ toxicity on the mice within a certain
treatment period, major organs including heart, liver, kidney and spleen
from experimental mice administered with free ixazomib and
ixazomib-treatment were sectioned and stained with HE. No obvious
histopathological change was observed in heart, lung and spleen of
ixazomib treated mice, as shown in Figure 7 D. No significant
drug-related effects on body weight or any other signs of overt toxicity
were shown in the group (Figure 7F). Collectively, these results
suggested that ixazomib was an effective and safe anti-tumor drug in
ESCC.