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新型姜黄素纳米制剂诱导肝癌细胞凋亡,并减少其迁移和血管生成。

Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells.

机构信息

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):361-370. doi: 10.1080/21691401.2023.2238756.

Abstract

BACKGROUND

Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity.

METHODS

Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells.

RESULTS

The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL ( < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis ( < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells.

CONCLUSION

Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

摘要

背景

姜黄素已被用于治疗多种疾病;然而,其较低的药理学特性降低了其治疗用途。为了提高其生物活性,出现了纳米制剂。因此,我们旨在确定是否用 PEG/壳聚糖包覆的姜黄素纳米粒(Cur-NPs)能改善肝癌(LC)细胞的治疗效果,并阐明其抗癌活性的潜在分子机制。

方法

以 Cur-PLGA-PEG/壳聚糖 NPs 的形式合成 Cur-NPs。在 HepG2 和 Huh 7 LC 细胞和 THLE-2 正常肝细胞中评估 Cur-NPs 的作用。

结果

合成的 Cur-NPS 的大小确定在标准范围内为 141.2 ± 47.5nm。与 THLE-2 细胞相比,LC 细胞在 48 小时后用 6.25μg/mL 的 Cur-NPs 处理时表现出细胞毒性。用 2.5μg/mL 的 Cur-NPs 处理 HepG-2 细胞抑制细胞迁移,而在 10μg/mL 时这种抑制作用增强( < 0.001)。用 5μg/mL 的 Cur-NPs 处理鸡胚减少了 4 日龄胚胎的血管生成( < 0.001)。纳米制剂以浓度依赖的方式上调 Bax 和 p53,并下调 Bcl-2,随后诱导 HepG-2 细胞凋亡。

结论

用 Cur-NPs 处理 LC 细胞可降低细胞增殖、迁移和血管生成,并通过促进促凋亡途径诱导细胞死亡。

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