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负载姜黄素的乳粒纳米颗粒通过p53信号通路诱导胰腺癌细胞系PANC-1凋亡。

Curcumin-loaded emulsome nanoparticles induces apoptosis through p53 signaling pathway in pancreatic cancer cell line PANC-1.

作者信息

Demirci Zuleyha, Islek Zeynep, Siginc Halime Ilhan, Sahin Fikrettin, Ucisik Mehmet H, Bolat Zeynep Busra

机构信息

Experimental Medicine Research and Application Center, Validebag Research Park, University of Health Sciences, 34662 Istanbul, Uskudar, Türkiye; Department of Chemistry, Faculty of Art and Science, Yildiz Technical University, 34220 Istanbul, Türkiye.

Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Kayisdagi Cad., 34755 Atasehir, Istanbul, Türkiye.

出版信息

Toxicol In Vitro. 2025 Jan;102:105958. doi: 10.1016/j.tiv.2024.105958. Epub 2024 Oct 21.

Abstract

Pancreatic cancer is a global health problem with a poor prognosis, limited treatment options and low survival rates of patients. Thus, the exploration of novel treatment approaches is crucial. Curcumin shows promise in pancreatic cancer. Curcumin has anticancer properties promoting apoptosis through the p53 pathway. However, adverse effects and low bioavailability are curcumin's main drawbacks and its delivery by nanoparticles could improve its effectiveness as a treatment option. Curcumin-loaded emulsome nanoparticles (CurEm) have shown promise in colorectal, hepatocellular, and prostate cancers. This study aims to evaluate the anticancer potential of CurEm in pancreatic cancer cell line PANC-1. The cytotoxic effects of CurEm on PANC-1 cells show cytotoxicity in dose and time-dependent manner. The selected dose 30 μM CurEm resulted spheroidal morphology in PANC-1 cells and colony forming and scratch assay conducted demonstrated significant growth inhibition and decrease in migration ability, respectively. Cell cycle analysis shows that CurEm induces G2/M arrest in PANC-1 cells. CurEm-treated PANC-1 cells showed a significant increase in p53 and Caspase 3 genes, while a significant decrease in Bcl-2 genes compared to untreated group. Western blot results showed parallel results to qPCR analysis for Bcl-2 protein levels. Interestingly, we saw low p53 protein levels in CurEm-treated PANC-1 cells. These findings shed light on the potential of CurEm as an effective and stable therapeutic approach for pancreatic cancer.

摘要

胰腺癌是一个全球性的健康问题,预后较差,治疗选择有限,患者生存率低。因此,探索新的治疗方法至关重要。姜黄素在胰腺癌治疗中显示出前景。姜黄素具有抗癌特性,可通过p53途径促进细胞凋亡。然而,副作用和低生物利用度是姜黄素的主要缺点,通过纳米颗粒递送可以提高其作为治疗选择的有效性。载有姜黄素的乳剂纳米颗粒(CurEm)在结直肠癌、肝细胞癌和前列腺癌中已显示出前景。本研究旨在评估CurEm在胰腺癌细胞系PANC-1中的抗癌潜力。CurEm对PANC-1细胞的细胞毒性作用呈剂量和时间依赖性。选择的30μM CurEm剂量导致PANC-1细胞呈球形形态,进行的集落形成和划痕试验分别显示出显著的生长抑制和迁移能力下降。细胞周期分析表明,CurEm诱导PANC-1细胞发生G2/M期阻滞。与未处理组相比,CurEm处理的PANC-1细胞中p53和Caspase 3基因显著增加,而Bcl-2基因显著减少。蛋白质印迹结果显示与Bcl-2蛋白水平的qPCR分析结果一致。有趣的是,我们在CurEm处理的PANC-1细胞中看到低水平的p53蛋白。这些发现揭示了CurEm作为一种有效且稳定的胰腺癌治疗方法的潜力。

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