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一种针对结直肠癌干细胞的新型治疗方法:用咖啡酸阻断PI3K/Akt信号轴

A Novel Therapeutic Approach for Colorectal Cancer Stem Cells: Blocking the PI3K/Akt Signaling Axis With Caffeic Acid.

作者信息

Park Se-Ra, Kim Soo-Rim, Hong In-Sun, Lee Hwa-Yong

机构信息

Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences & Technology (GAIHST), Gachon University, Incheon, South Korea.

Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, South Korea.

出版信息

Front Cell Dev Biol. 2020 Dec 23;8:585987. doi: 10.3389/fcell.2020.585987. eCollection 2020.

Abstract

Cancer stem cells (CSCs) have been identified in a multiple of cancer types and resistant to traditional cancer therapies such as chemotherapeutic agents and radiotherapy, which may destroy bulk tumor cells but not all CSCs, contributing to reformation tumor masses and subsequent relapse. Moreover, it is very difficult to effectively identify and eliminate CSCs because they share some common phenotypic and functional characteristics of normal stem cells. Therefore, finding better therapeutic strategies to selectively target CSCs might be helpful to reduce subsequent malignancies. In the present study, we found that caffeic acid effectively suppresses self-renewal capacity, stem-like characteristics, and migratory capacity of CD44 and CD133 colorectal CSCs and . In addition, we also revealed that PI3K/Akt signaling may be linked to multiple colorectal CSC-associated characteristics, such as radio-resistance, stem-like property, and tumorigenic potential. To the best of our knowledge, this is the first study demonstrating that caffeic acid effectively targets colorectal CSC populations by inhibiting the growth and/or self-renewal capacity of colorectal CSCs through PI3K/Akt signaling and .

摘要

癌症干细胞(CSCs)已在多种癌症类型中被鉴定出来,并且对传统癌症治疗方法如化疗药物和放疗具有抗性,这些传统疗法可能会破坏大部分肿瘤细胞,但并非所有癌症干细胞,从而导致肿瘤块的重新形成和随后的复发。此外,很难有效识别和消除癌症干细胞,因为它们具有一些正常干细胞共有的表型和功能特征。因此,找到更好的治疗策略来选择性地靶向癌症干细胞可能有助于减少后续的恶性肿瘤。在本研究中,我们发现咖啡酸能有效抑制CD44和CD133结直肠癌干细胞的自我更新能力、干细胞样特性和迁移能力。此外,我们还揭示PI3K/Akt信号通路可能与多种结直肠癌干细胞相关特征有关,如抗辐射性、干细胞样特性和致瘤潜力。据我们所知,这是第一项证明咖啡酸通过PI3K/Akt信号通路抑制结直肠癌干细胞的生长和/或自我更新能力,从而有效靶向结直肠癌干细胞群体的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77ec/7785810/465f1dcd2953/fcell-08-585987-g001.jpg

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