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Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways

Wang, Ying-Chun MD; Wu, Yi-Nan MD; Wang, Su-Li MD; Lin, Qing-Hua PhD; He, Ming-Fang PhD; Liu, Qiao-lin PhD; Wang, Jin-Hua PhD

International Journal of Gynecological Cancer: July 2016 - Volume 26 - Issue 6 - p 994–1003
doi: 10.1097/IGC.0000000000000746
Basic Science

Objective: We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3).

Methods: Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish.

Results: Docosahexaenoic acid and α-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but α-linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01).

Conclusions: Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-κB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy.

*Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, Nanjing Medical University; †China Pharmaceutical University; ‡Nanjing University of Technology School of Pharmaceutical Science; §Department of Obstetrics and Gynecology, Jiangning Hospital, Nanjing Medical University; and ∥Jinling Hospital, Nanjing University, Nanjing, China.

Address correspondence and reprint requests to Jinhua Wang, PhD, Department of Gynecological Oncology Surgery, Jiangsu Cancer Hospital & Institute, 42 Baiziting Rd, Nanjing, Jiangsu 210009, China. E-mail: wangjinhua588@163.com.

Supported by grants from National Science Foundation (81473636); Jiangsu Government Scholarship “333” Plan, Jiangsu Key Medical Personnel (RC2011091); and Chinese Post-Doctor Program (2013M542578).

The authors declare no conflicts of interest.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Received July 1, 2015

Received in revised form March 23, 2016

Accepted March 28, 2016

© 2016 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.