Arginine inhibits the malignant transformation induced by interferon gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo
Arginine inhibits the malignant transformation induced by interferon gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo
复制标题
精氨酸通过 NF-kappa B-GCN2/eIF2 α 信号通路抑制体内外乳腺上皮细胞中干扰素 γ 诱导的恶性转化
DOI：
10.1016/j.yexcr.2018.05.003
复制
发表时间：
2018-07-15
影响因子：
3.7
通讯作者：
Lei, Liancheng
中科院分区：
文献类型：
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作者：
Ren, Wenbo;Li, Yang;Lei, Liancheng
乳腺癌是世界上最常见的女性恶性肿瘤。它严重影响妇女的身心健康，是妇女癌症死亡的主要原因。我们以前的研究表明，饮食来源的IFN-γ促进原代牛乳腺上皮细胞的恶性转化，通过加速精氨酸消耗。本研究旨在探讨精氨酸是否能抑制肿瘤细胞的恶性转化程度及其分子机制。结果表明，精氨酸的添加可以减轻由IFN-γ诱导的乳腺上皮细胞的恶性转化，包括减少细胞增殖、细胞迁移和集落形成，通过NF-κ B-GCN 2/eIF 2 α途径。体内实验也一致证实，补充精氨酸可以显着抑制荷瘤小鼠的肿瘤生长。此外，临床数据的调查还显示，人乳腺癌患者的血浆或组织中精氨酸水平低于良性乳腺疾病患者，而IFN-γ水平高于良性乳腺疾病患者，表明IFN-γ可能是潜在的控制靶点。我们的研究结果表明，精氨酸补充剂可以拮抗IFN-γ（营养诱导）诱导的乳腺上皮细胞的恶性转化在体外和体内，和IFN-γ是在乳腺癌妇女更高。这可能为乳腺癌的预防和治疗提供一种新的营养策略。
Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-gamma promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-gamma, including reducing cell proliferation, cell migration and colony formation, through the NF-kappa B-GCN2/elF2 alpha pathway. The in vivo experiments also consistently confirmed that arginine supplementation could significantly inhibit tumor growth in tumor-bearing mice. Furthermore, the investigation of the clinical data also revealed that the plasma or tissue from human breast cancer patients owned lower arginine level and higher IFN-gamma level than that from patients with benign breast disease, showing IFN-gamma may be a potential control target. Our findings demonstrate that arginine supplement could antagonize the malignant transformation of mammary epithelial cells induced by IFN-gamma (nutritionally induced) both in vitro and in vivo, and IFN-gamma was higher in breast cancer women. This might provide a novel strategy for the prevention and treatment of breast cancer regarding to nutrition.