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急性髓系白血病靶向纳米脂质体对JAK/STAT3表达的抑制作用以增强化疗效果

Inhibition of JAK/STAT3 Expression by Acute Myeloid Leukemia-Targeted Nanoliposome for Chemotherapy Enhancement.

作者信息

Zuo Yao, Li Hongwen, Wang Xiaochao, Liang Yejin, Huang Caihong, Nai Guanye, Ruan Jingrong, Dong Wenzheng, Lu Xiang

机构信息

Department of Hematology & Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi 533000, P. R. China.

Department of Hematology, The First People's Hospital of Nanning, Guangxi 530022, P. R. China.

出版信息

ACS Omega. 2024 Aug 28;9(36):37901-37909. doi: 10.1021/acsomega.4c00710. eCollection 2024 Sep 10.

Abstract

Acute myeloid leukemia (AML) is a relatively common malignant hematological disease whose development is mostly associated with abnormal activation of the JAK/STAT3 signaling pathway. Our previous study revealed that SAR317461, a novel JAK2/STAT3 inhibitor, can effectively inhibit the activation of the JAK2/STAT3 signaling pathway and has significant damaging and pro-apoptotic effects on AML cell lines. This project aims to build upon our prior research to enhance the application of SAR317461 in AML. The surface modification of liposomes with the CD34 antibody, along with the inclusion of the SAR317461 and cytarabine (a common AML chemotherapeutic agent), is observed. Due to the high expression of CD34 on the surface of AML cells, the nanoliposome could target AML cells specifically, further achieving an effective treatment for AML through the synergistic effect of JAK2/STAT3 inhibitors and chemotherapeutic agents. The implementation of this project will provide more theoretical support and ideas for the clinical application of JAK/STAT3 inhibitors in malignant tumors and for overcoming chemotherapy resistance.

摘要

急性髓系白血病(AML)是一种相对常见的恶性血液疾病,其发展大多与JAK/STAT3信号通路的异常激活有关。我们之前的研究表明,新型JAK2/STAT3抑制剂SAR317461能够有效抑制JAK2/STAT3信号通路的激活,并且对AML细胞系具有显著的破坏和促凋亡作用。本项目旨在基于我们之前的研究,加强SAR317461在AML中的应用。观察到用CD34抗体对脂质体进行表面修饰,并加入SAR317461和阿糖胞苷(一种常用的AML化疗药物)。由于AML细胞表面CD34的高表达,纳米脂质体可以特异性地靶向AML细胞,通过JAK2/STAT3抑制剂和化疗药物的协同作用进一步实现对AML的有效治疗。本项目的实施将为JAK/STAT3抑制剂在恶性肿瘤中的临床应用以及克服化疗耐药性提供更多的理论支持和思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/594c/11391460/7c05221f7a8f/ao4c00710_0001.jpg

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