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Neamine Inhibits Tumor Growth In a Mouse Model of Colitis-Associated Cancer
Alexander Hu
1, James Yoo
1 1 Brigham and Women's Hospital, Boston, MA
Background: We have previously shown that angiogenin, a 14-kDa ribonuclease, regulates colitis severity and tumor growth in a mouse model of colitis-associated cancer (CAC). The aim of this study was to determine whether pharmacologic inhibition of angiogenin can be used therapeutically in CAC.
Methods: Wild-type (WT) C57BL/6 mice (n=27) were given azoxymethane (AOM), a colon carcinogen, 2 days in advance of two cycles of 3.5% dextran sodium sulfate (DSS). Neamine (30 mg/kg, IP every 3 days), an angiogenin inhibitor, was given starting on day 0 (n=5), after the 1st DSS cycle (n=8), and after the 2nd DSS cycle (n=7). Disease activity index (DAI) was recorded, and mice were euthanized after the 2nd DSS cycle and were compared to control mice (n=7).
Results: The administration of neamine was associated with more severe colitis during the recovery phase of colitis but led to a significant reduction in tumor number (control: 16.9 ± 9.5; neamine: 10.6 ± 5.3, p=0.038). Mice given neamine at baseline (10.0 ± 3.4 tumors), after the 1st DSS cycle (10.63 ± 5.7) and after the 2nd DSS cycle (10.86 ± 6.5) all developed fewer tumors compared to the control group. The effectiveness of neamine to suppress tumor growth diminished when administered late vs. early.
Conclusion: The angiogenin inhibitor neamine worsens colitis but decreases tumor growth in a mouse model of CAC. These findings mirror the phenotypic responses of Ang1-KO mice to AOM-DSS and suggest that targeted inhibition of angiogenin may be a novel therapeutic strategy for CAC.
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