Mohamed Hanan R H, Hakeem George M, Latif Yasmin Abdel, Elnawasani Shahd H, Nagy Maria, Mohamed Basma A, Essam Rawan, Safwat Gehan
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.
Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), 6th of October City, Egypt.
Sci Rep. 2025 Jun 20;15(1):20144. doi: 10.1038/s41598-025-05088-9.
Pancreatic cancer is a hard-to-treat tumor with a poor prognosis. While traditional pancreatic cancer therapies can be effective, issues like cytotoxicity, low selectivity, and drug resistance still pose major challenges. Nanotechnology has shown promise in improving cancer diagnosis and treatment. Yttrium oxide nanoparticles (YO-NPs), for example, have demonstrated potent selective cytotoxicity against triple negative breast cancer cells; but their effects on pancreatic cancer cells have not been explored. This study aimed to explore the impact of YO-NPs on cell proliferation, DNA integrity, and oxidative stress in pancreatic cancer (PANC-1) and human skin fibroblast (HSF) cells. The cytotoxicity of YO-NPs after 72 h were estimated using Sulforhodamine (SRB) cytotoxicity assay, while alkaline Comet assay was done to study genomic DNA integrity. Generation level of reactive oxygen species (ROS) and integrity of mitochondrial membrane potential were also analyzed. Apoptosis induction was investigated using Flow Cytometry and expression level of apoptotic (p53), anti-apoptotic (Bcl2) and mitochondrial (ND3) genes was measured using quantitative RTPCR. Our findings exhibited that YO-NPs had strong selective cytotoxicity against PANC-1 cells with an IC50 value of 31.06 µg/ml, while having minimal effect on normal HSF cells (IC50 = 319.21 µg/ml). Treatment of PANC-1 cells with YO-NPs at the IC50 concentration for 72 h significantly increased intracellular ROS levels and DNA damage, along with a notable reduction in mitochondrial membrane potential. Additionally, a significant rise in necrotic, early, and late apoptotic cells was observed, accompanied by downregulation of the anti-apoptotic Bcl2 gene and upregulation of the apoptotic p53 and mitochondrial ND3 genes. These findings highlight the selective toxicity of YO-NPs towards cancerous PANC-1 cells, with minimal impact on normal cells. YO-NPs appear to induce apoptosis in cancer cells by increasing ROS generation, damaging DNA, disrupting mitochondrial function, and triggering cell death. This study suggests that YO-NPs may be a promising candidate for pancreatic cancer treatment. Further research is needed to fully explore their therapeutic potential.
胰腺癌是一种难以治疗且预后较差的肿瘤。虽然传统的胰腺癌治疗方法可能有效，但细胞毒性、低选择性和耐药性等问题仍然构成重大挑战。纳米技术在改善癌症诊断和治疗方面已显示出前景。例如，氧化钇纳米颗粒（YO-NPs）已证明对三阴性乳腺癌细胞具有强大的选择性细胞毒性；但它们对胰腺癌细胞的影响尚未得到探索。本研究旨在探讨YO-NPs对胰腺癌（PANC-1）细胞和人皮肤成纤维细胞（HSF）的细胞增殖、DNA完整性和氧化应激的影响。使用磺酰罗丹明（SRB）细胞毒性测定法评估72小时后YO-NPs的细胞毒性，同时进行碱性彗星试验以研究基因组DNA完整性。还分析了活性氧（ROS）的生成水平和线粒体膜电位的完整性。使用流式细胞术研究凋亡诱导情况，并使用定量RTPCR测量凋亡（p53）、抗凋亡（Bcl2）和线粒体（ND3）基因的表达水平。我们的研究结果表明，YO-NPs对PANC-1细胞具有强烈的选择性细胞毒性，IC50值为31.06μg/ml，而对正常HSF细胞的影响最小（IC50 = 319.21μg/ml）。用IC50浓度的YO-NPs处理PANC-1细胞72小时，可显著增加细胞内ROS水平和DNA损伤，同时线粒体膜电位显著降低。此外，观察到坏死、早期和晚期凋亡细胞显著增加，同时抗凋亡Bcl2基因下调，凋亡p53和线粒体ND3基因上调。这些发现突出了YO-NPs对癌性PANC-1细胞的选择性毒性，对正常细胞影响最小。YO-NPs似乎通过增加ROS生成、损伤DNA、破坏线粒体功能和触发细胞死亡来诱导癌细胞凋亡。本研究表明，YO-NPs可能是胰腺癌治疗的一个有前景的候选药物。需要进一步研究以充分探索其治疗潜力。
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