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.