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非离子表面活性剂囊泡包封的山奈酚对MCF-7乳腺癌细胞的凋亡和抗转移作用

The apoptotic and anti-metastatic effects of niosome kaempferol in MCF-7 breast cancer cells.

作者信息

Minaei Shinoo, Kavousi Mahsa, Jamshidian Faranak

机构信息

Department of Biology, ET.C., Islamic Azad University, Tehran, Iran.

出版信息

Sci Rep. 2025 Jul 1;15(1):20741. doi: 10.1038/s41598-025-07221-0.

Abstract

Kaempferol (KMF) possesses notable anti-tumor bioactivity, which indicates its promising action in the therapy of gynecologic cancers. Here, we examined the therapeutic potential of the naturally occurring flavonoid kaempferol coated on niosome nanoparticles (NPs) and its impact on the breast cancer cell line MCF-7. Niosome NPs containing KMF were prepared by thin-layer hydration. The generated niosome/KMF NPs cytotoxicity on MCF-7 and MCF-10 cell lines were assessed by MTT assay. The physicochemical properties of the niosome/KMF NPs were characterized by SEM, DLS zeta potential, and FTIR. Flow cytometry was used to quantify primary and secondary apoptosis, necrosis and cell cycle arrest. Finally, the expression of apoptosis (Bax and caspase 3) and metastasis genes (ITGA5 and MMP2) was analyzed by Real-time PCR. A Scratch test was performed to investigate the anti-metastatic effect of synthesized nanoparticles. The results showed that the synthesized niosome/KMF NPs have a diameter of 500 nm, a zeta potential of 33.9 mV and a PDI of 0.169. The FTIR spectrum of niosome NPs containing KMF showed distinct peaks in the range of 600-3400 cm belonging to different components. The results of the MTT assay showed that treatment of the MCF-7 cell line with a concentration of 0.0873 µMol of niosome NPs containing KMF resulted in the death of 50% of the cells. Niosome/KMF NPs caused 64% apoptosis in MCF-7 cells. Real-time PCR results showed a 2.95- and 2.75-fold increase in Bax and caspase 3 gene expression compared to the control group (p < 0.001). After 72 h of treatment with niosome NPs containing KMF, ITGA5 and MMP2 gene expression decreased by 0.58- and 0.53-fold, respectively (p < 0.001). In summary, KMF-loaded niosome NPs efficiently induced apoptosis and inhibited metastasis-related gene expression in MCF-7 cells, exhibiting notable anti-cancer activity.

摘要

山奈酚(KMF)具有显著的抗肿瘤生物活性,这表明其在妇科癌症治疗中具有潜在作用。在此,我们研究了包覆在脂质体纳米颗粒(NPs)上的天然类黄酮山奈酚的治疗潜力及其对乳腺癌细胞系MCF-7的影响。通过薄膜水化法制备了含有KMF的脂质体NPs。采用MTT法评估所生成的脂质体/KMF NPs对MCF-7和MCF-10细胞系的细胞毒性。通过扫描电子显微镜(SEM)、动态光散射(DLS)ζ电位和傅里叶变换红外光谱(FTIR)对脂质体/KMF NPs的物理化学性质进行了表征。采用流式细胞术对原发性和继发性凋亡、坏死及细胞周期阻滞进行定量分析。最后,通过实时定量聚合酶链反应(Real-time PCR)分析凋亡基因(Bax和半胱天冬酶3)和转移基因(整合素α5(ITGA5)和基质金属蛋白酶2(MMP2))的表达。进行划痕试验以研究合成纳米颗粒的抗转移作用。结果表明,合成的脂质体/KMF NPs直径为500 nm,ζ电位为33.9 mV,多分散指数(PDI)为0.169。含有KMF的脂质体NPs的FTIR光谱在600 - 3400 cm范围内显示出属于不同成分的明显峰。MTT试验结果表明,用浓度为0.0873 µmol的含有KMF的脂质体NPs处理MCF-7细胞系,导致50%的细胞死亡。脂质体/KMF NPs在MCF-7细胞中引起64%的凋亡。实时定量聚合酶链反应结果显示,与对照组相比,Bax和半胱天冬酶3基因表达分别增加了2.95倍和2.75倍(p < 0.001)。用含有KMF的脂质体NPs处理72小时后,ITGA5和MMP2基因表达分别下降了0.58倍和0.53倍(p < 0.001)。总之,负载KMF的脂质体NPs在MCF-7细胞中有效诱导凋亡并抑制转移相关基因表达,表现出显著的抗癌活性。

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