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Kenpaullone 通过抑制 KLF4 诱导 B-NHL 细胞系产生细胞毒性和化疗增敏作用,与 YY1 无关。

KLF4 inhibition by Kenpaullone induces cytotoxicity and chemo sensitization in B-NHL cell lines via YY1 independent.

机构信息

Molecular Signal Pathway in Cancer Laboratory, UIMEO, Oncology Hospital, Siglo XXI National Medical Center, IMSS, México City, México.

Unidad de Posgrado, Facultad de Medicina Universidad Nacional Autónoma de México, México City, México.

出版信息

Leuk Lymphoma. 2021 Jun;62(6):1422-1431. doi: 10.1080/10428194.2020.1869960. Epub 2021 Jan 7.

Abstract

Krüppel-like factor 4 (KLF4) is a member of the KLF transcription factor family containing zinc-fingers, and is involved in the regulation of apoptosis, proliferation and differentiation of B cells and B-cell malignancies. KLF4 can act like an oncogene, we shown that KLF4 overexpression correlated with poor prognostic and chemoresistance in B-NHL. In addition, we shown that KLF4 is regulated by YY1. In this study, we demonstrate that chemical inhibition of KLF4 by Kenpaullone, results in suppression of proliferation, cell survival, downregulation of Bcl-2 and increases apoptosis in B-NHL cell lines through YY1 independent pathway. Combination of Kenpaullone and Doxorubicin, increased apoptosis. The co-expressions of KLF4/YY1 or KLF4/Bcl-2 in NHL was analyzed using Oncomine Database, exhibiting a positive correlation of expression. The present findings suggest that the chemical inhibition of KLF4 by Kenpaullone treatment could be a potential therapeutic alternatively in KLF4 lymphomas.

摘要

Krüppel 样因子 4(KLF4)是含锌指的 KLF 转录因子家族的成员,参与 B 细胞和 B 细胞恶性肿瘤的凋亡、增殖和分化的调节。KLF4 可以像癌基因一样发挥作用,我们的研究表明 KLF4 过表达与 B-NHL 的不良预后和化疗耐药相关。此外,我们还表明 KLF4 受 YY1 调节。在这项研究中,我们通过 YY1 非依赖性途径证明,通过 Kenpaullone 化学抑制 KLF4 可抑制 B-NHL 细胞系的增殖、细胞存活、下调 Bcl-2 并增加细胞凋亡。Kenpaullone 和阿霉素联合使用可增加细胞凋亡。使用 Oncomine 数据库分析 NHL 中 KLF4/YY1 或 KLF4/Bcl-2 的共表达,显示出表达的正相关。这些发现表明,通过 Kenpaullone 处理化学抑制 KLF4 可能是 KLF4 淋巴瘤的一种潜在治疗选择。

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