Erianin inhibits the progression of pancreatic cancer by directly targeting AKT and ASK1.

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2024-10-25 DOI:10.1186/s12935-024-03533-9

Ruxue Liu, Minghan Qiu, Xinxin Deng, Meng Zhang, Zhanhua Gao, Yayun Wang, Hanwei Mei, Mengting Zhai, Qiaonan Zhang, Jie Hao, Zhen Yang, Huaqing Wang

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引用次数: 0

Abstract

Background: Pancreatic cancer is a malignant tumor of the digestive tract with a high mortality rate. Erianin has antitumor activity, but the regulatory targets and mechanism of action in pancreatic cancer are unclear. The objective of this study was to evaluate the anti-pancreatic cancer activity of Erianin and explore its underlying mechanisms.

Methods: A network pharmacology approach was used to investigate the mechanism of action of Erianin in pancreatic cancer cells. Cell proliferation was analyzed using CCK8, colony-formation, and EdU proliferation assays. Cell migration was evaluated through wound healing and transwell assays, as well as determination of the protein expression levels of EMT markers and β-catenin. Apoptosis and the cell cycle were measured using flow cytometry and JC-1 staining, respectively. The protein expression levels of p-Rb, CyclinB1, P21, Cleaved-PARP, and Cleaved-Caspase3 were assessed using western blotting. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to elucidate the mechanism underlying the action of Erianin in pancreatic cancer. Western blotting was used to examine the expression levels of key proteins in the AKT, JNK, and p38 MAPK signaling pathways. Molecular docking and CETSA were used to test hypotheses. The tumor-suppressive ability of Erianin in vivo was assessed using a tumor-bearing assay in nude mice.

Results: Network pharmacology revealed that Erianin inhibited pancreatic cancer through multiple pathways. Erianin significantly inhibited pancreatic cancer cell proliferation and migration while promoting intracellular ROS and inducing apoptosis. Mechanistically, Erianin inhibited pancreatic cancer cell proliferation by regulating the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. In vivo experiments showed that Erianin inhibited subcutaneous tumor growth and promoted tumor tissue apoptosis in nude mice.

Conclusions: The component-target-pathway network revealed that Erianin exerted anti-cancer effects through multiple components, targets, and pathways. Erianin inhibited the proliferation and migration of pancreatic cancer cells and induced apoptosis through the AKT/FOXO1 and ASK1/JNK/p38 MAPK signaling pathways. These results indicate that Erianin is a promising agent for pancreatic cancer treatment.

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Erianin 可直接靶向 AKT 和 ASK1，从而抑制胰腺癌的进展。

背景：胰腺癌是一种死亡率很高的消化道恶性肿瘤。Erianin 具有抗肿瘤活性，但其在胰腺癌中的调控靶点和作用机制尚不清楚。本研究旨在评估 Erianin 的抗胰腺癌活性并探索其潜在机制：方法：采用网络药理学方法研究 Erianin 在胰腺癌细胞中的作用机制。细胞增殖采用 CCK8、集落形成和 EdU 增殖试验进行分析。通过伤口愈合和透孔试验评估了细胞迁移，并测定了 EMT 标记物和β-catenin 的蛋白表达水平。细胞凋亡和细胞周期分别通过流式细胞术和 JC-1 染色法进行测定。p-Rb、CyclinB1、P21、Cleaved-PARP和Cleaved-Caspase3的蛋白表达水平采用Western印迹法进行评估。进行了 RNA 测序（RNA-seq）和生物信息学分析，以阐明 Erianin 在胰腺癌中的作用机制。采用 Western 印迹法检测 AKT、JNK 和 p38 MAPK 信号通路中关键蛋白的表达水平。分子对接和 CETSA 被用来检验假设。使用裸鼠肿瘤实验评估了 Erianin 在体内的肿瘤抑制能力：结果：网络药理学显示，Erianin通过多种途径抑制胰腺癌。Erianin 能明显抑制胰腺癌细胞的增殖和迁移，同时促进细胞内 ROS 的生成并诱导细胞凋亡。从机理上讲，Erianin 通过调节 AKT/FOXO1 和 ASK1/JNK/p38 MAPK 信号通路抑制胰腺癌细胞增殖。体内实验表明，Erianin能抑制裸鼠皮下肿瘤生长，促进肿瘤组织凋亡：结论：成分-靶点-通路网络显示，Erianin通过多种成分、靶点和通路发挥抗癌作用。Erianin 通过 AKT/FOXO1 和 ASK1/JNK/p38 MAPK 信号通路抑制胰腺癌细胞的增殖和迁移，并诱导细胞凋亡。这些结果表明，Erianin 是一种很有前景的胰腺癌治疗药物。

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

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.