Li Feng, Song Xiaoyun, Zhou Xiqiu, Chen Lili, Zheng Jinzhou
Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 Wanpingnan Road, Shanghai, 200032, China.
Heliyon. 2023 Jun 7;9(6):e17052. doi: 10.1016/j.heliyon.2023.e17052. eCollection 2023 Jun.
Emodin, a natural anthraquinone derivative, can inhibit lipid synthesis and breast cancer cell proliferation. We previously found that emodin decreased breast cancer liver metastasis via epithelial-to-mesenchymal transition (EMT) inhibition. However, the mechanism through which emodin affects breast cancer liver metastasis in high-fat diet-induced obese and hyperlipidemic mice has not been elucidated. Bioinformatics analysis was used to reveal the potential targets and pathways of emodin. The mouse model of liver metastasis was established by injecting breast cancer cells into the left ventricle in high-fat diet-induced obese mice. The effect of emodin on inhibiting liver metastasis of breast cancer was evaluated by animal experiments. The mechanisms through which emodin inhibits liver metastasis of breast cancer were studied by cell and molecular biological methods. Emodin reduced lipid synthesis by inhibiting the expression of triglyceride (TG) synthesis-related genes, such as fatty acid synthase (Fasn), glycerol-3-phosphate acyltransferase 1 (Gpat1), and stearoyl-CoA desaturase (Scd1), and ultimately reduced liver metastasis in breast cancer. In addition, emodin inhibited breast cancer cell proliferation and invasion through the serine/threonine kinase (AKT) signaling and extracellular-regulated protein kinase (ERK) pathways by interacting with CSNK2A1, ESR1, ESR2, PIM1 and PTP4A3. Our results indicate that emodin may have therapeutic potential in the prevention or treatment of breast cancer liver metastasis.
大黄素是一种天然蒽醌衍生物，可抑制脂质合成和乳腺癌细胞增殖。我们之前发现大黄素通过抑制上皮-间质转化（EMT）减少乳腺癌肝转移。然而，大黄素在高脂饮食诱导的肥胖和高脂血症小鼠中影响乳腺癌肝转移的机制尚未阐明。利用生物信息学分析揭示大黄素的潜在靶点和途径。通过将乳腺癌细胞注射到高脂饮食诱导的肥胖小鼠的左心室中建立肝转移小鼠模型。通过动物实验评估大黄素对抑制乳腺癌肝转移的作用。采用细胞和分子生物学方法研究大黄素抑制乳腺癌肝转移的机制。大黄素通过抑制甘油三酯（TG）合成相关基因如脂肪酸合酶（Fasn）、甘油-3-磷酸酰基转移酶1（Gpat1）和硬脂酰辅酶A去饱和酶（Scd1）的表达来减少脂质合成，最终减少乳腺癌的肝转移。此外，大黄素通过与酪蛋白激酶2α1（CSNK2A1）、雌激素受体1（ESR1）、雌激素受体2（ESR2）、原癌基因丝氨酸/苏氨酸激酶（PIM1）和蛋白酪氨酸磷酸酶4A3（PTP4A3）相互作用，通过丝氨酸/苏氨酸激酶（AKT）信号通路和细胞外调节蛋白激酶（ERK）信号通路抑制乳腺癌细胞的增殖和侵袭。我们的结果表明，大黄素在预防或治疗乳腺癌肝转移方面可能具有治疗潜力。
