Targeting cell signaling pathway ALKBH5/Beclin1/ULK1 in lung cancer by 5-flurouracil- loaded P (AAm/SA) nanogel in rats.

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Apoptosis Pub Date : 2025-05-01 DOI:10.1007/s10495-025-02102-3

Ahmad S Kodous, Eman S Eldin, Hebatallah E Mohamed, Mohamed Mohamady Ghobashy, Dina F El-Maghraby

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引用次数: 0

Abstract

Purpose: Lung cancer is the second most common Cancer in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. 5-fluorouracil (5-FU) is among the most administrated chemotherapeutic agents for various neoplasms. This study focused on synthesizing and characterizing P(AAm/SA)/5-Fu nanogels as a potential drug delivery system.

Methods: The nanogels were prepared by combining sodium alginate (SA) and acrylamide (AAm) monomers, followed by gamma irradiation-induced polymerization at a dose of 5 kGy. Then, the obtained nanogel was loaded with 500 ppm of 5-Fu. Transmission electron microscopy (TEM) imaging was utilized to characterize the nanogels' morphology and monodispersity with a particle size of (50 nm). Rats were randomly assigned to four groups (six animals per group): Group 1: (Control): normal healthy. Group 2: Cancer-bearing animals (animals injected with diethylnitrosamine (DEN) 20 mg/kg body weight for 3 months. Group 3: Cancer+ 5-fluorouracil (12 mg/kg body weight). Group4: Cancer+ 5-Flurouracil- Loaded P (AAm/SA) Nanogel.

Results: DEN markedly increased PTGS2, Cox2, PKB, PFKm, and ERK1 levels. Also, observed up-regulation in ALKBH5, Beclin1, ULK1, and P53 gene expressions in the cancer-bearing animal group compared with the control group. 5-fluorouracil nano gel significantly ameliorated the above-mentioned parameters and immunohistochemistry study. 5-fluorouracil nanogel significantly ameliorated the parameters mentioned above, as well as the immunohistochemistry study.

Conclusion: The 5-FU-loaded P(AAm/SA) nanogel could serve as a promising approach for targeting tumor cell proliferation, speeding up autophagic processes, and overcoming chemotherapy resistance in lung carcinoma.

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5-氟尿嘧啶负载P （AAm/SA）纳米凝胶靶向肺癌细胞信号通路ALKBH5/Beclin1/ULK1

目的：肺癌是美国第二大常见癌症；然而，它仍然是美国和全世界癌症相关死亡的主要原因。5-氟尿嘧啶（5-FU）是各种肿瘤最常用的化疗药物之一。本研究的重点是合成和表征P(AAm/SA)/5-Fu纳米凝胶作为一种潜在的药物递送系统。方法：将海藻酸钠（SA）与丙烯酰胺（AAm）单体结合制备纳米凝胶，在5 kGy的辐照下进行聚合。然后，将得到的纳米凝胶负载500 ppm的5-Fu。利用透射电子显微镜（TEM）表征了粒径为（50 nm）的纳米凝胶的形貌和单分散性。将大鼠随机分为四组（每组6只）：第一组：（对照）：正常健康。第二组：荷瘤动物（注射二乙基亚硝胺（DEN） 20 mg/kg体重3个月）。第三组：癌症+ 5-氟尿嘧啶（12毫克/公斤体重）。第4组：癌症+ 5-氟尿嘧啶负载P （AAm/SA）纳米凝胶。结果：DEN显著提高PTGS2、Cox2、PKB、PFKm和ERK1水平。与对照组相比，荷瘤动物组ALKBH5、Beclin1、ULK1和P53基因表达上调。5-氟尿嘧啶纳米凝胶明显改善了上述参数和免疫组化研究。5-氟尿嘧啶纳米凝胶显著改善上述参数，以及免疫组织化学研究。结论：5- fu负载P（AAm/SA）纳米凝胶可作为靶向肺癌细胞增殖、加速自噬过程和克服化疗耐药的一种有前景的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Apoptosis 生物-生化与分子生物学

CiteScore

9.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.