(P13-045-23) Combining Gamma-Tocopherol (γT) and Aspirin Synergistically Suppresses Colitis-Associated Colon Tumorigenesis and Modulates Gut Microbiota in Mice

Objectives: Our objective is to explore the combinatory effects of gamma-tocopherol(γT) and aspirin on the development of colitis-associated colorectal cancer (CAC). We hypothesize that combining γT and aspirin is better than either compound singly for suppressing CAC.

Methods: AIN93G diets supplemented with aspirin (250ppm), or γT (500ppm) or their combination were given to AOM/DSS treated male Balb/c mice for 9 weeks. Histopathological analysis and multiplex-based immunoassay of cytokines were conducted using colon tissues collected. Gut microbiome were analyzed based 16S rRNA sequencing followed by QIIME2 analysis using feces collected. Cell viability was examined using MTT assay.

Results: Compared to the control, combining aspirin and γT but not either compound alone significantly reduced AOM/DSS-induced tumor area and multiplicity of large-size tumors by 60% and 50%, respectively. Meanwhile, γT mitigated aspirin-promoted inflammation and stomach lesions in mice. Moreover, the combination appeared to cause favorable changes of gut microbiota compared to the control and synergistically suppressed the growth of HCT116 cells.

Conclusions: Our study demonstrates that combining aspirin and γT improves anticancer effects and counteracted side effects compared to aspirin and may therefore be a novel combinatory chemopreventive agent against CAC.

Funding Sources: Purdue Research Foundation, USDA Hatch 1022869
Purdue University Center for Cancer Research, NIH grant for P30CA023168.