Medium‐chain fatty acids (MCFAs) have 6–12 carbon atoms and are instantly absorbed into the bloodstream before traveling to the portal vein and the liver, where they are immediately used for energy and may have antitumor effects. Its role in breast cancer is poorly understood. To investigate the apoptosis‐inducing effect of MCFAs in breast cancer cells, cell viability assay, colony formation assay, cell migration assay, cell invasion assay, nuclear morphology, cell cycle assay, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), apoptosis, RT‐qPCR analysis, and Western blot analysis were performed. In the present study, MCFA treatments reduced proliferative capability, increased ROS level, increased the depletion of MMP, induced G0/G1 and S phase cell cycle arrest, and late apoptosis of breast cancer cells in an effective concentration. Besides, MCFA treatment contributed to the upregulation of proapoptotic protein (BAK) and caspase‐3, and the downregulation of antiapoptotic protein (Bcl‐2). Mechanistically, phosphorylation levels of EGFR, Akt, and mTOR were significantly reduced in breast cancer cells treated with MCFAs. However, no significant changes in apoptosis and signaling‐related proteins were observed in lauric acid‐treated ER‐positive cancer cells. Our findings suggested that MCFAs suppressed breast cancer cell proliferation by modulating the PI3K/Akt/mTOR signaling pathway. MCFAs may be a promising therapeutic drug for treating breast cancer.

中文翻译：

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中链脂肪酸通过抑制 Akt/mTOR 通路和调节 Bcl-2 家族蛋白对人乳腺癌细胞增殖的抑制作用

中链脂肪酸 (MCFA) 具有 6-12 个碳原子，在进入门静脉和肝脏之前立即被吸收到血液中，在那里它们立即被用作能量，并可能具有抗肿瘤作用。它在乳腺癌中的作用尚不清楚。为了研究MCFAs对乳腺癌细胞的凋亡诱导作用，细胞活力测定、集落形成测定、细胞迁移测定、细胞侵袭测定、核形态、细胞周期测定、细胞内活性氧（ROS）、基质金属蛋白酶（MMP） 、细胞凋亡、RT-qPCR 分析和蛋白质印迹分析。在本研究中，MCFA治疗在有效浓度下降低了乳腺癌细胞的增殖能力，增加了ROS水平，增加了MMP的消耗，诱导G0/G1和S期细胞周期停滞，以及晚期凋亡。此外，MCFA 治疗还导致促凋亡蛋白 (BAK) 和 caspase-3 上调，以及抗凋亡蛋白 (Bcl-2) 下调。从机制上讲，用 MCFA 处理的乳腺癌细胞中 EGFR、Akt 和 mTOR 的磷酸化水平显着降低。然而，在月桂酸处理的 ER 阳性癌细胞中，没有观察到细胞凋亡和信号相关蛋白的显着变化。我们的研究结果表明，MCFA 通过调节 PI3K/Akt/mTOR 信号通路来抑制乳腺癌细胞增殖。 MCFA 可能是一种有前途的治疗乳腺癌的药物。