Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies.
Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies.
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非瑟酮通过调节 PI3K/Akt/mTOR 通路对乳腺癌细胞的抗癌作用：体外和体内研究
DOI：
10.3892/ijmm.2018.3654
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发表时间：
2018-08
影响因子：
5.4
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Sun X;Ma X;Li Q;Yang Y;Xu X;Sun J;Yu M;Cao K;Yang L;Yang G;Zhang G;Wang X
非瑟酮是一种天然黄酮类化合物，广泛存在于多种食用和药用植物中，具有抑制多种肿瘤细胞增殖和诱导细胞凋亡的作用。然而，非瑟酮对乳腺癌的影响很少有报道，其潜在的机制仍不清楚。本研究旨在探讨非瑟酮对乳腺癌细胞的抑制作用及其机制。MTT法检测非瑟酮对4 T1、MCF-7和MDA-MB-231细胞生长的影响。采用细胞增殖阵列、伤口愈合实验和基于细胞-基质阻抗传感平台的HUV-EC-C-细胞屏障实验，评价非瑟酮对4 T1细胞增殖、迁移和侵袭的抑制作用。流式细胞仪检测细胞凋亡情况，Western blotting检测靶分子。使用4 T1原位乳腺肿瘤模型来评估非瑟酮对体内肿瘤生长的抑制。使用试剂盒检测荷瘤小鼠的肝和肾功能。结果表明，非瑟酮在体外抑制乳腺癌细胞的增殖，抑制4 T1细胞的转移和侵袭，并诱导4 T1细胞的凋亡。非瑟酮的强效抗癌作用与调节磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶点通路有关。体内实验表明，非瑟酮抑制4 T1细胞来源的原位乳腺肿瘤的生长，并促进肿瘤细胞凋亡，和评估的丙氨酸氨基转移酶和天冬氨酸氨基转移酶在荷瘤小鼠血清中的水平表明，非瑟酮可能会导致对肝脏生化功能的副作用。本研究证实非瑟酮具有抗乳腺癌作用。然而，体内实验也显示非瑟酮溶解度低，生物利用度低。需要进一步的调查，以确定非瑟酮的临床价值。
Fisetin, a natural flavonoid found in a variety of edible and medical plants, has been suggested to inhibit the proliferation of various tumor cells and to induce apoptosis. However, the effects of fisetin on breast cancer have rarely been reported and the underlying mechanism is still undefined. The present study explored the anti-cancer effects of fisetin on mammary carcinoma cells and the underlying mechanisms. Following treatment with fisetin, viability of 4T1, MCF-7 and MDA-MB-231 cells were measured by MTT assay. The inhibitory effects of fisetin on proliferation, migration and invasion were evaluated in 4T1 cells using proliferation array, wound-healing assay, and HUV-EC-C-cell barrier based on electrical cell-substrate impedance sensing platform. Cell apoptosis was analyzed by flow cytometry, and western blotting analysis was performed to identify target molecules. A 4T1 orthotopic mammary tumor model was used to assess the fisetin-inhibition on tumor growth in vivo. Test kits were used to examine the liver and kidney function of tumor-bearing mice. The results suggest that fisetin suppressed the proliferation of breast cancer cells, suppressed the metastasis and invasiveness of 4T1 cells, and induced the apoptosis of 4T1 cells in vitro. The potent anti-cancer effect of fisetin was associated with the regulation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In vivo experiments demonstrated that fisetin suppressed the growth of 4T1 cell-derived orthotopic breast tumors and enhanced tumor cell apoptosis, and the evaluated alanine amino transferase and aspartate amino transferase levels in serum of tumor-bearing mice suggested that fisetin may lead to side effects on liver biochemical function. The present study confirms that fisetin exerted an anti-mammary carcinoma effect. However, in vivo experiments also revealed that fisetin had low solubility and low bioavailability. Further investigation is required to determine the clinical value of fisetin.
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影响因子：
28.2
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
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通过将 HPβCD 封装在聚合物纳米颗粒中，提高非瑟酮的口服生物利用度和抗癌功效。
影响因子：
6
作者：
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通讯作者：
Sistla R