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富含 DHA/EPA 的磷脂酰胆碱通过激活过氧化物酶体增殖物激活受体 γ 抑制 Lewis 肺癌小鼠的肿瘤生长和转移。

DHA/EPA-Enriched Phosphatidylcholine Suppresses Tumor Growth and Metastasis via Activating Peroxisome Proliferator-Activated Receptor γ in Lewis Lung Cancer Mice.

机构信息

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, Shandong, China.

Marine Biomedical Research Institute of Qingdao, Qingdao 266061, Shandong, China.

出版信息

J Agric Food Chem. 2021 Jan 20;69(2):676-685. doi: 10.1021/acs.jafc.0c06890. Epub 2021 Jan 6.

Abstract

In the present study, the antitumor effects of docosahexaenoic acid-phosphatidylcholine (DHA-PC) and eicosapentanoic acid-phosphatidylcholine (EPA-PC) in Lewis lung cancer mice were investigated. As observed, DHA-PC and EPA-PC obviously inhibited the transplanted tumor growth and the positive expression of Ki67. The metastatic nodules and hematoxylin and eosin (HE) staining of the lung indicated that DHA-PC and EPA-PC suppressed lung metastasis. PPARγ has a key role in cell survival, which may be a target for cancer therapy. Further mechanism research indicated that DHA-PC and EPA-PC significantly enhanced the levels of PPARγ and subsequently downregulated the NF-κB pathway. DHA-PC and EPA-PC accelerate cancer cell apoptosis by decreasing NF-κB-mediated antiapoptotic factors Bcl-2 and Bcl-XL, thereby inhibiting tumor growth. In addition, DHA-PC and EPA-PC significantly decreased the levels of NF-κB-mediated matrix metallopeptidase 9 (MMP9) and heparanase (HPA), which block the extracellular matrix (ECM) degradation, thereby suppressing lung metastasis. These findings suggested that DHA-PC and EPA-PC could be used as food supplements and/or functional ingredients for cancer patients.

摘要

在本研究中,研究了二十二碳六烯酸-磷脂酰胆碱(DHA-PC)和二十碳五烯酸-磷脂酰胆碱(EPA-PC)在 Lewis 肺癌小鼠中的抗肿瘤作用。结果表明,DHA-PC 和 EPA-PC 明显抑制移植瘤生长和 Ki67 的阳性表达。肺转移结节和苏木精和伊红(HE)染色表明 DHA-PC 和 EPA-PC 抑制肺转移。过氧化物酶体增殖物激活受体γ(PPARγ)在细胞存活中起关键作用,可能是癌症治疗的靶点。进一步的机制研究表明,DHA-PC 和 EPA-PC 显著增加了 PPARγ 的水平,随后下调了 NF-κB 通路。DHA-PC 和 EPA-PC 通过降低 NF-κB 介导的抗凋亡因子 Bcl-2 和 Bcl-XL 来促进癌细胞凋亡,从而抑制肿瘤生长。此外,DHA-PC 和 EPA-PC 显著降低了 NF-κB 介导的基质金属蛋白酶 9(MMP9)和乙酰肝素酶(HPA)的水平,阻断细胞外基质(ECM)降解,从而抑制肺转移。这些发现表明,DHA-PC 和 EPA-PC 可用作癌症患者的膳食补充剂和/或功能性成分。

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