Targeting ARPC1B⁺ Cancer Stem Cells to Sensitise Pancreatic Cancer to Gemcitabine Treatment.

IF 5.6 1区生物学 Q2 CELL BIOLOGY

Cell Proliferation Pub Date : 2025-09-03 DOI:10.1111/cpr.70125

Yang Wu, Jianpeng Zhang, Weixiong Zhu, Xinrui Zhu, Yi Liu, Xin Wang, Tianyu Zhao, Chun Zhang, Zili Zhang, Wenjie Shi, Run Shi, Zhaokai Zhou, Shaohui Xu

引用次数: 0

Abstract

ARPC1B⁺ cancer stem cells (CSCs) in pancreatic cancer are identified as a subpopulation resistant to gemcitabine. In our study, drug repositioning, molecular docking, and surface plasmon resonance (SPR) technique jointly revealed that CK-636 can directly target ARPC1B protein with high affinity. In vitro cytotoxicity, ex vivo organoid cultures, in vivo xenograft and orthotopic gemcitabine-resistant pancreatic cancer model demonstrated that combination therapy of gemcitabine plus CK-636 showed a superior anti-tumor effect compared with gemcitabine monotherapy. Our study demonstrated that CK-636 can act as a rational adjuvant to overcome gemcitabine resistance in pancreatic cancer therapy.

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靶向ARPC1B+肿瘤干细胞使胰腺癌对吉西他滨治疗敏感

胰腺癌中的ARPC1B+癌症干细胞（CSCs）被确定为对吉西他滨耐药的亚群。在我们的研究中，通过药物重定位、分子对接和表面等离子体共振（SPR）技术共同揭示了CK-636可以高亲和力地直接靶向ARPC1B蛋白。体外细胞毒性、体外类器官培养、体内异种移植和原位吉西他滨耐药胰腺癌模型表明，吉西他滨联合CK-636治疗比吉西他滨单药治疗具有更好的抗肿瘤效果。我们的研究表明，CK-636可以作为一种合理的佐剂，在胰腺癌治疗中克服吉西他滨耐药。

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

Cell Proliferation 生物-细胞生物学

CiteScore

14.80

自引率

2.40%

发文量

198

审稿时长

1 months

期刊介绍： Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.

Targeting ARPC1B+ Cancer Stem Cells to Sensitise Pancreatic Cancer to Gemcitabine Treatment.

Abstract

Targeting ARPC1B⁺ Cancer Stem Cells to Sensitise Pancreatic Cancer to Gemcitabine Treatment.