Abstract 1901: Endogenous increase of omega-3 polyunsaturated fatty acids through expression of of ω3-desaturase gene inhibits tumorigenicity and metastasis of prostate cancer cells in vitro and in vivo

Abstract

Abstract The ω3-desaturase (Fat-1) catalyzes the conversion ω6-polyunsaturated fatty acids (ω6-PUFAs) to ω3 polyunsaturated fatty acids (ω3-PUFAs) and increases the amount of ω3-PUFAs. It is known that ω3-PUFAs have anti-tumorigenic properties, while ω6-PUFAs accelerate tumorigenesis. Here, we report that endogenous increase of omega-3 polyunsaturated fatty acids through expression of fat-1 gene may inhibit tumorigenicity and metastasis of prostate cancer cells in vitro and in vivo. When mouse prostate cancer RM1 cells were implanted into mice, tumor size and volume were significantly reduced in Fat-1 transgenic mice (Fat-1 transgenic mice express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously.) compared with wild mice. In immunohistochemical analysis of tumors tissue of Fat-1 mice, apoptotic cells were markedly increased and angiogenesis significantly was reduced, compared with wild mice tumor. When RM1 cells were injected through tail vein, lung metastasis of RM1 cells was significantly inhibited in Fat-1 transgenic mice. On the other hand, the fat-1 stable RM1 cells (fRM1sc) were significantly inhibited the proliferation compared to the cells expressing the control vector (fRM1cc) and fRM1sc showed an increase in the proportion of cells in G2/M phase comparing with fRM1cc. Tumor growth of fRM1sc implanted into C57BL6 control mice was significantly decreased, and tumor tissues from fRM1sc implanted-animals showed an increase in the apoptotic index compared to fRM1cc. Moreover, the proliferation index and microvessel density were significantly decreased. Furthermore, transwell chamber assay for invasion indicated a reduction of cell invasion in the human prostate fPC3sc when compared with the fRM1cc. In Zymography, MMP-9 and MMP-2 activties were decrease in fPC3sc. These results suggest that expression of the fat-1 gene, thereby enhancing endogenous levels of ω3-PUFAs may prevent tumorigenicity and metastasis of prostate cancer cells. Additionally, transgenic mouse and a stable cell line of fat-1 gene are useful to study the anti-cancer effects of ω3-PUFAs. [This research was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (No. 2007-0054932)] Citation Format: Soyeon Shin, Kaipeng Jing, Soyeon Jeong, Soyeon Kim, Yifan Dai, Tong Wu, Jun-Young Heo, Seung-Kiel Park, Gi-Ryang Kweon, Jong-Il Park, Kyu Lim. Endogenous increase of omega-3 polyunsaturated fatty acids through expression of of ω3-desaturase gene inhibits tumorigenicity and metastasis of prostate cancer cells in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1901. doi:10.1158/1538-7445.AM2015-1901