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载姜黄素(BNE)PLGA 纳米粒诱导人 MCF-7 乳腺癌细胞发生早期坏死性凋亡和晚期凋亡。

The Extract (BNE)-Loaded PLGA Nanoparticles as an Early Necroptosis and Late Apoptosis Inducer in Human MCF-7 Breast Cancer Cells.

机构信息

Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.

出版信息

Nutr Cancer. 2022;74(7):2540-2549. doi: 10.1080/01635581.2021.2008986. Epub 2021 Nov 30.

Abstract

Loading of the extract (BNE) on PLGA nanoparticle (BNE-PNP) and study its necroptotic activity in human MCF7-breast cancer cells. Double emulsion solvent evaporation methods were used for synthesis of BNE-PNP and DLS, SEM, and surface Zeta-potential analysis were applied for defining the physicochemical properties of BNE-PNP. The cytotoxic impact of BNE-PNP nanoparticles was analyzed by MTT assay and expression of apoptotic (P53 and Cas-3) and necrotic (TNF-α) gene markers were measured by qPCR to evaluate the BNE-PNP-induced cell death type. The stable (-36.07 mV) BNE-PNP were synthesized at 71.07 nm dimension. They significantly decrease the count of metabolically active MCF7 cells (IC: 170.94 µg/ml after 48 h). The BNE-PNP induced an early programmed necrotic (necroptosis) and late apoptotic death on the MCF7 cancer cells by up-regulating all the P53/TNF-α and Cas-3 gene expression, respectively. The BNE-PNP dose-dependently induced an early cell-selective necroptotic death. Since the necroptotic death is known as a biocompatible cellular death induction, the BNE-PNP have the potential to be used as a safe efficient anticancer compound.

摘要

将提取物 (BNE) 加载到 PLGA 纳米颗粒 (BNE-PNP) 上,并研究其在人 MCF7-乳腺癌细胞中的坏死性细胞凋亡活性。采用双乳液溶剂蒸发法合成 BNE-PNP,并应用 DLS、SEM 和表面 Zeta 电位分析来定义 BNE-PNP 的物理化学性质。通过 MTT 测定分析 BNE-PNP 纳米颗粒的细胞毒性作用,并通过 qPCR 测量凋亡 (P53 和 Cas-3) 和坏死 (TNF-α) 基因标志物的表达,以评估 BNE-PNP 诱导的细胞死亡类型。合成了稳定的 (-36.07 mV) BNE-PNP,其粒径为 71.07nm。它们在 48 小时后显著降低 MCF7 细胞的代谢活性计数 (IC:170.94µg/ml)。BNE-PNP 通过上调所有 P53/TNF-α 和 Cas-3 基因的表达,分别诱导 MCF7 癌细胞早期程序性坏死(坏死性细胞凋亡)和晚期凋亡死亡。BNE-PNP 呈剂量依赖性诱导早期细胞选择性坏死性细胞凋亡。由于坏死性细胞凋亡被认为是一种生物相容性的细胞死亡诱导,因此 BNE-PNP 有可能被用作安全有效的抗癌化合物。

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