Article Publish Status: FREE
Abstract Title:

Elevation ofω-3 Polyunsaturated Fatty Acids Attenuates PTEN-deficiency Induced Endometrial Cancer Development through Regulation of COX-2 and PGE2 Production.

Abstract Source:

Sci Rep. 2015;5:14958. Epub 2015 Oct 15. PMID: 26468779

Abstract Author(s):

Jinshun Pan, Lixian Cheng, Xinyun Bi, Xin Zhang, Shanshan Liu, Xiaoming Bai, Fanghong Li, Allan Z Zhao

Article Affiliation:

Jinshun Pan

Abstract:

Endometrial cancer is one of the most common gynecologic malignancies. Phosphatase and tensin homologue (PTEN)-mutation is frequently identified in endometrial cancer patients. Although high dietary intake ofω-3 polyunsaturated fatty acids (PUFAs) has been associated with reduced risk of endometrial cancer, the underlying mechanisms is still unknown. To this end, we evaluated the impact of ω-3 PUFAs using several endometrial cancer cellular and animal models. While ~27% and 40% of heterozygotic PTEN mutant mice developed endometrial cancer and atypical complex hyperplasia, respectively, none of the PTEN(+/-) mice developed cancer when we overexpressed an mfat-1 transgene, which allowed endogenous production of ω-3 PUFAs. Fish oil-enriched diet or expression of mfat-1 transgene significantly inhibited the growth of xenograft tumor derived from RL95-2 cells bearing a PTEN null mutation. At cellular level, ω-3 PUFAs treatment decreased the viability of RL95-2 cells, AKT phosphorylation, and cyclin D1 expression. These molecular events are primarily mediated through reduction of cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. Exogenous PGE2 treatment completely blunted the impact of ω-3 PUFAs on endometrial cancer. Thus, we revealed the direct inhibitory effects of ω-3 PUFAs on endometrial cancer development and the underlying mechanisms involving reduction of COX-2 and PGE2.

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