(P12-023-25) Alternating Supplementation of Aspirin and Delta-Tocotrienol Inhibited Tumor Development in a Murine Model Resembling Early-Stage Colorectal Cancer

Objectives: Colorectal cancer (CRC) is a leading cause of cancer death. Chemoprevention with effective and relatively safe compounds is important for inhibiting CRC progression and thus reducing CRC associate mortality. While non-steroid anti-inflammatory drugs (NSAIDs) including aspirin have been recognized as promising chemopreventive agents against CRC, they often show modest efficacy with side effects. We recently showed that delta-tocotrienol δTE), a member in the vitamin E family, can target different CRC-promoting pathways compared to aspirin and blocked tumors in a colitis associated colon cancer model. Therefore, we hypothesize that δTE and aspirin may work together to improve anti-CRC outcomes. The objective of our current study is to assess the effect of alternating supplementation of aspirin and δTE on tumor development in a CRC model where tumors are driven by colonic epithelial gene mutations including Apc and Kras in mice.

Methods: We used 41 Apc^+/580S, Kras^+/LSL, CAC (AKC) mice which bear a deletion in the Apc gene and expression of mutant Kras gene in the colon. The mice were randomly assigned into two groups according to age- and body weight-matching. The control group received a control diet (AIN-93G), while the treatment group received dTE-supplement diet (δTE/γTE (8/1), 0.08% diet) or aspirin-supplement (0.05% aspirin) diet at an alternating week schedule. After 4-week intervention, the mice were euthanized and tumor development were evaluated.

Results: There were no differences in tumor incidence between the control and the combination diet groups. Compared to the control diet group, the dTE+aspirin group had lowered colon weight (0.48±0.05 vs. 0.34±0.03 (ctrl), p = 0.028), enhanced colon length-to-weight ratio (26.40±3.13 vs. 18.09±1.93 (ctrl), p</em> = 0.010), and reduced total tumor area (24.72±5.64 vs. 48.22±7.18 (ctrl), p</em> = 0.026).

Conclusions: Alternating supplementation of aspirin and delta-tocotrienol inhibited tumor development in a mouse model resembling early-stage sporadic CRC.

Funding Sources: NIH/NCI R03CA283236-01A1, USDA Hatch 1022869, PICR pilot funding