Abstract
Our previous report showed that concomitant supplementation of lycopene and eicosa-pentaenoic acid synergistically inhibited the proliferation of human colon cancer HT-29 cells in vitro. To validate our findings, the present study investigated whether consumption of lycopene and fish oil would help prevent tumor growth and progression in a mouse xenograft model of colon cancer. The inhibitory effects of lycopene and fish oil on tumor growth were verified by western blotting analysis, bioluminescent imaging, immunohistochemical (IHC) staining and ELISA. The results demonstrated that lycopene and fish oil synergistically inhibited the growth of colon cancer in tumor-bearing mice. The bioluminescent imaging, histopathological and IHC staining results indicated that lycopene and fish oil effectively suppressed tumor growth and progression of colon cancer in vivo. The chemopreventive effects of lycopene and fish oil were associated with augmented expression of the cell cycle inhibitors such as p21(CIP1/WAF1) and p27(Kip1) , and suppression of proliferating cell nuclear antigen, β-catenin, cyclin D1 and c-Myc proteins. Furthermore, lycopene and fish oil inhibited tumor progression through suppression of MMP-7, MMP-9, COX-2 and PGE2. These results show that lycopene and fish oil act synergistically as chemopreventive agents against tumor growth and progression in a mouse xenograft model of colon cancer.
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