研究动态
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Dorema aucheri 提取物和姜黄素的纳米脂质体共封装;增强口腔癌细胞 OCC-02 中的细胞毒性、细胞凋亡诱导和 EGFR 基因表达抑制。

Nanoliposomal Coencapsulation of Dorema aucheri Extract and Curcumin; Enhanced Cytotoxicity, Apoptosis Induction, and Inhibition of EGFR Gene Expression in Oral Cancer Cells OCC-02.

发表日期:2023
作者: Mahshid Azizi, Ghasem Ghalamfarsa, Fatemeh Khosravani, Hassan Bardania, Shahriar Azizi
来源: Cell Death & Disease

摘要:

姜黄素是天然抗癌药物之一,但其有效性受到稳定性低、生物利用度不足、溶解性差和渗透性差的限制。 Dorema aucheri (Bilhar) 是一种具有珍贵药用特性的草药。本研究旨在开发基于纳米脂质体的姜黄素和 Bilhar 提取物共传递系统。采用脂质薄膜水化法合成纳米化合物,并通过透射电子显微镜和动态光散射技术进行表征,并通过2,5-二苯基-2H-四唑评估其对原代口腔癌细胞系的细胞毒性和凋亡作用溴化物测定和流式细胞术。此外,使用实时聚合酶链式反应技术评估了处理细胞中表皮生长因子受体(EGFR)基因的表达。结果表明,纳米脂质体的尺寸为91±10nm,多分散指数为0.13。游离姜黄素、提取物以及姜黄素-提取物组合对癌细胞表现出剂量依赖性毒性;然而,提取物(IC50:86μg/ml)和姜黄素提取物(IC50:65μg/ml)的活性远高于姜黄素(IC50:121μg/ml)。此外,装载在脂质体上的姜黄素和提取物显示出剂量和时间依赖性的细胞毒性。将姜黄素提取物化合物负载到纳米脂质体上后,其 IC50 从 180μg/ml(24 小时内)降至 43μg/ml(72 小时内),表明其可持续释放和活性。同样,该化合物在癌细胞中诱导最高的凋亡百分比(95%),并抑制细胞中 EGFR 基因的表达达 81%±3%。这些发现证明了 Bilhar 提取物对抗口腔癌细胞的有效性。此外,与姜黄素结合后,它显示出附加活性,在装载到纳米脂质体上后显着改善。版权所有 © 2023 Mahshid Azizi 等人。
Curcumin is one of the natural anticancer drugs but its efficiency is limited by low stability, insufficient bioavailability, poor solubility, and poor permeability. Dorema aucheri (Bilhar) is a herb with precious pharmaceutical properties. This study aimed to develop a nanoliposome-based curcumin and Bilhar extract codelivery system. The nanocompounds were synthesized using the lipid thin-film hydration method and characterized by transmission electron microscopy, and dynamic light scattering techniques, and their cytotoxicity and apoptotic effect on the primary oral cancer cell line were evaluated via 2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. Moreover, the expression of the epidermal growth factor receptor (EGFR) gene in the treated cells was assessed using the real-time polymerase chain reaction technique. Based on the results, nanoliposomes had a size of 91 ± 10 nm with a polydispersity index of 0.13. Free curcumin, the extract, and the curcumin-extract combination showed dose-dependent toxicity against cancer cells; yet, the extract (IC50: 86 µg/ml) and curcumin-extract (IC50: 65 µg/ml) activities were much more than curcumin (IC50: 121 µg/ml). Also, the curcumin and extract loaded on liposomes showed a dose and time-dependent cytotoxicity. After loading the curcumin-extract compound on nanoliposomes, their IC50 decreased from 180 µg/ml (within 24 hr) to 43 µg/ml (within 72 hr), indicating their sustainable release and activity. Likewise, this compound induced the highest apoptosis percentage (95%) in cancerous cells and inhibited the expression of the EGFR gene in the cells by 81% ± 3%. These findings demonstrated the effectiveness of the Bilhar extract against oral cancer cells. Also, in combination with curcumin, it showed an additive activity that considerably improved after loading on nanoliposomes.Copyright © 2023 Mahshid Azizi et al.