Fenofibrate, a PPAR α agonist, inhibits the growth of a murine colon adenocarcinoma in vivo
Avraham Belizon, Patrick K. Horst, Irena Kirman, Emre Balik, H M. Shantha Kumara, Suvinit Jain, Richard L. Whelan; Surgery, Columbia University Medical Center, New Hyde Park, NY
Purpose: Recent literature has suggested that peroxisome proliferator activated receptor (PPAR) agonists may have a role in preventing tumor growth and spread. There are a number of PPAR subtypes; including α, β, γ, and δ. Although some studies have shown that PPAR agonists inhibit angiogenesis and induce apoptosis in multiple tumor cell lines, there is little data about PPAR α agonists. PPAR α agonists are of interest because they may inhbit angiogenesis and also inhibit the release of MMP-9, which has been implicated in tumor spread. Our goal was to examine the effects of fenofibrate(FF), a PPAR alpha agonist, on tumor cell growth in a colon cancer murine model. Methods: 37 8 weeks old C57BL/6 mice were included in this study. 19 mice received daily gavage of FF(100mg/kg) dissolved in 100% vegetable oil. 18 mice received daily gavage of placebo (100% vegetable oil). Mice were gavaged for a total of 24 days. On day number 13, all mice underwent subcutaneous implantation of 20,000 MC-38 tumor cells under the dorsal skin. Tumor size was assessed by measuring the furthest distance from end to end and multiplying it by its perpendicular distance. On day 25 the mice were sacrificed and tumors were excised, measured, and weighed. Results: 10 mice in the FF group and 3 mice in the placebo group died between days 13-15. Of the mice that survived, the FF group had a significantly lower incidence of tumor implantation when compared to the placebo group (44% vs. 80%; p<0.05). In addition the tumors that did implant were significantly smaller than the corresponding tumor size in the placebo group(6.84 mm2 vs. 25.5mm2; p<0.05). The tumor weights were also significantly lower in the FF group when compared to the placebo group(8.89mg vs. 52mg ; p<0.05). Conclusions: Despite a high mortality rate, fenofibrate a PPAR alpha agonist, inhibited murine colonic tumor growth and implantation in this model. Further studies are necessary to evaluate its mechanism of action. In addition, our high mortality rate may be due to the duration of treatment as well as the mode of delivery. Future experiments are needed to evaluate the mortality following a shorter duration treatment, as well as different routes of administration.
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