Abstract 1301: Anti-invasive and antimetastatic effects of 3-polyunsaturated fatty acids through inhibition of NF-kBmatrix metalloproteinases in ovarian cancer cells

Ovarian cancer is leading cause of gene cological cancer death in the United States. It is reported that about 14,000 patients will die to ovarian cancer in United States, 2015. 3- and 6-PUFAs are considered as essential fatty acids because they cannot be synthesized in mammals. The 3-desaturase (fat-1) converts 6-PUFAs to 3-PUFAs. Cancer cells and transgenic mice stably expressing fat-1 geneare useful models to study the anti-cancer effects of 3-PUFAs. Here, we show anti-invasive and anti-metastatic action of 3-PUFA in ovarian cancer.DHA significantly inhibited cell invasion and wound healing activity of human ovarian PA-1 cells. DHA also abolishedthe induction of matrix-metalloproteinases (MMPs) and cyclooxygenase (COX2) as well as the transactivity of NF-B in PA-1 cells. When ID8 cells were subcutaneously implanted into fat-1 transgenic mice, the tumor size and volume were smallin comparison to wild-type mice. The growth inhibition of tumor was also confirmed with the increase in the level of TUNEL-positive cells. Additionally, when ID8 cells were injected via tail vein of fat1 mice, the lung metastasis was remarkably inhibited in fat-1 transgenic mice. Furthermore, the proliferation of fat-1-stably expressing PA-1 (f-PA-1) cells was more attenuated than that of cells expressing control vectors. The invasion and NF-BMMPs promoter activities were also decreased in f-PA-1 cells. These results suggest that 3-PUFAs inhibit invasion and metastasis of ovarian cancer cells through inhibition of NF-BMMPs. Therefore, 3-PUFAs may contribute an effective and safe therapeutic approach for the chemoprevention and treatment of human ovarian cancer. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (2007-0054932)