Background: w-3 FA have anti-inflammatory and tumor growth inhibitory effects that may be used clinically to attenuate tumor growth and cachexia syndrome. The inducible enzyme cyclooxygenase-2 (COX-2) is an important mediator of angiogenesis and tumor growth. The purpose of this study was to examine the tumor-specific and treatment-specific effects of supplemental dietary w-3 fatty acid and a selective COX-2 inhibitor (rofecoxib) in an animal model of progressive malignancy.
Methods: Male Sprague Dawley rats (300-350 g) were randomly divided into ten treatment groups. From days 1 to 14, gavage pre-treatment feedings was performed with either w-3 fatty acid (1cc, 5.0g/kg/d); corn oil (1cc), and saline (1cc) with or without rofecoxib(1cc) as shown in table 1 to five of the groups (pre-implant). All rats underwent flank implantation of the methycholantrene (MCA)-induced fibrosarcoma on day 14. Post-implantation gavage feeding was performed as described earlier to all groups from days 15 through 42 (Pre and post implant)). All animals from each group were weighed at the beginning of the experiment and every two weeks thereafter. The animals were sacrificed on day 42, and the tumors were removed. The tumors were weighed and subtracted by the actual animal weight to obtain the carcass weight. The tumor weight was divided by the tumor-free carcass weight to obtain percentage of tumor volume. Parameters evaluated were tumor volume, weight loss/gain, carcass weight, tumor-carcass ratio, and tumor growth rate.
Results/Conclusion: Animals supplemented with w-3 fatty acids continuously throughout the study demonstrated a reduction in overall tumor volume (figure below), a similar although less marked reduction was also noted for rofecoxib and combination treated groups. Similar results were observed for post-implant treatment with the same agents. Interestingly, the use of a combined w-3 and COX-2 inhibitor strategy in a continuous manner (pre and post) resulted in a significant reduction (P<0.004 graph not shown in overall tumor volume compared to post-only therapy. Based on previous observations of divergent immune regulation by these two agents, the potential clinical applications of this strategy merit further investigation.