Yun Eun-Jin, Song Kyung-Sub, Shin Soyeon, Kim Soyeon, Heo Jun-Young, Kweon Gi-Ryang, Wu Tong, Park Jong-Il, Lim Kyu
Department of Biochemistry, College of Medicine, Chungnam National University, Daejon 301-747, Republic of Korea.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Oncotarget. 2016 Aug 2;7(31):49961-49971. doi: 10.18632/oncotarget.10266.
Breast cancer is one of the most prevalent cancers in women, and nearly half of breast cancer patients develop distant metastatic disease after therapy. Despite the significant advances that have been achieved in understanding breast cancer metastasis in the past decades, metastatic cancer is still hard to cure. Here, we demonstrated an anti-cancer mechanism of docosahexaenoic acid (DHA) that suppressed lung metastasis in breast cancer. DHA could inhibit proliferation and invasion of breast cancer cells in vitro, and this was mainly through blocking Cox-2-PGE2-NF-κB-MMPs cascades. DHA treatment significantly decreased Cox-2 and NF-κB expression as well as nuclear translocation of NF-κB in MDA-MB-231 cells. In addition, DHA also reduced NF-κB binding to DNA which may lead to inactivation of MMPs. Moreover, in vivo studies using Fat-1 transgenic mice showed remarkable decrease of tumor growth and metastasis to EO771 cells to lung in DHA-rich environment. In conclusion, DHA attenuated breast cancer progression and lung metastasis in part through suppressing MMPs, and these findings suggest chemoprevention and potential therapeutic strategy to overcome malignant breast cancer.
乳腺癌是女性中最常见的癌症之一，近一半的乳腺癌患者在治疗后会发生远处转移性疾病。尽管在过去几十年中对乳腺癌转移的认识取得了重大进展，但转移性癌症仍然难以治愈。在此，我们展示了二十二碳六烯酸（DHA）抑制乳腺癌肺转移的抗癌机制。DHA在体外可抑制乳腺癌细胞的增殖和侵袭，这主要是通过阻断Cox-2-PGE2-NF-κB-MMPs级联反应实现的。DHA处理显著降低了MDA-MB-231细胞中Cox-2和NF-κB的表达以及NF-κB的核转位。此外，DHA还减少了NF-κB与DNA的结合，这可能导致MMPs失活。此外，使用Fat-1转基因小鼠的体内研究表明，在富含DHA的环境中，肿瘤生长和EO771细胞向肺的转移显著减少。总之，DHA部分通过抑制MMPs减轻了乳腺癌的进展和肺转移，这些发现提示了化学预防和克服恶性乳腺癌的潜在治疗策略。
