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Wnt 受体 1 抑制剂可抑制低剂量辐射诱导的 C6 GSCs 中 Wnt1、Wnt3a 和 β-连环蛋白对增殖和迁移的影响。

Inhibitor of Wnt receptor 1 suppresses the effects of Wnt1, Wnt3a and β‑catenin on the proliferation and migration of C6 GSCs induced by low‑dose radiation.

机构信息

Department of Human Anatomy, Basic Medical College, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750006, P.R. China.

The Second Affiliated Hospital of Xi'an Medical University Xi'an, Shaanxi 710038, P.R. China.

出版信息

Oncol Rep. 2024 Feb;51(2). doi: 10.3892/or.2023.8681. Epub 2023 Dec 15.


DOI:10.3892/or.2023.8681
PMID:38099414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10777445/
Abstract

The radioresistance of glioma is an important cause of treatment failure and tumor aggressiveness. In the present study, under performed with linear accelerator, the effects of 0.3 and 3.0 Gy low‑dose radiation (LDR) on the proliferation and migration of C6 glioma stem cells were examined by flow cytometric analysis, immunocytochemistry and western blot analysis. It was found that low‑dose ionizing radiation (0.3 Gy) stimulated the proliferation and migration of these cells, while 3.0 Gy ionizing radiation inhibited the proliferation of C6 glioma stem cells, which was mediated through enhanced Wnt/β‑catenin signaling, which is associated with glioma tumor aggressiveness. LDR treatment increased the expression of the DNA damage marker γ‑HAX but promoted cell survival with a significant reduction in apoptotic and necrotic cells. When LDR cells were also treated with an inhibitor of Wnt receptor 1 (IWR1), cell proliferation and migration were significantly reduced. IWR1 treatment significantly inhibited Wnt1, Wnt3a and β‑catenin protein expression. Collectively, the current results demonstrated that IWR1 treatment effectively radio‑sensitizes glioma stem cells and helps to overcome the survival advantages promoted by LDR, which has significant implications for targeted treatment in radioresistant gliomas.

摘要

脑胶质瘤的放射抵抗是治疗失败和肿瘤侵袭性的重要原因。在本研究中,采用直线加速器进行低剂量照射(LDR),通过流式细胞术分析、免疫细胞化学和 Western blot 分析,研究了 0.3 和 3.0 Gy 低剂量辐射(LDR)对 C6 神经胶质瘤干细胞增殖和迁移的影响。结果发现,低剂量电离辐射(0.3 Gy)刺激这些细胞的增殖和迁移,而 3.0 Gy 电离辐射抑制 C6 神经胶质瘤干细胞的增殖,这是通过增强 Wnt/β-连环蛋白信号转导介导的,与神经胶质瘤肿瘤侵袭性有关。LDR 处理增加了 DNA 损伤标志物 γ-HAX 的表达,但促进了细胞存活,凋亡和坏死细胞明显减少。当 LDR 细胞也用 Wnt 受体 1(IWR1)抑制剂处理时,细胞增殖和迁移明显减少。IWR1 处理显著抑制 Wnt1、Wnt3a 和 β-连环蛋白蛋白表达。总之,目前的结果表明,IWR1 治疗可有效放射增敏神经胶质瘤干细胞,并有助于克服 LDR 促进的生存优势,这对放射抵抗性神经胶质瘤的靶向治疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/2c8d4e345310/or-51-02-08681-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/b68162a2aac7/or-51-02-08681-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/17b2e9a51f63/or-51-02-08681-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/70a371533623/or-51-02-08681-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/4e973c3638eb/or-51-02-08681-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/d2e3e38b4db9/or-51-02-08681-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/fe3f85e49d49/or-51-02-08681-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/d8df4b55bf2e/or-51-02-08681-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/2c8d4e345310/or-51-02-08681-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/b68162a2aac7/or-51-02-08681-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/17b2e9a51f63/or-51-02-08681-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/70a371533623/or-51-02-08681-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/4e973c3638eb/or-51-02-08681-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/d2e3e38b4db9/or-51-02-08681-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/fe3f85e49d49/or-51-02-08681-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/d8df4b55bf2e/or-51-02-08681-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62d3/10777445/2c8d4e345310/or-51-02-08681-g07.jpg

相似文献

[1]
Inhibitor of Wnt receptor 1 suppresses the effects of Wnt1, Wnt3a and β‑catenin on the proliferation and migration of C6 GSCs induced by low‑dose radiation.

Oncol Rep. 2024-2

[2]
PER2 inhibits proliferation and stemness of glioma stem cells via the Wnt/β‑catenin signaling pathway.

Oncol Rep. 2020-8

[3]
LGR5, a novel functional glioma stem cell marker, promotes EMT by activating the Wnt/β-catenin pathway and predicts poor survival of glioma patients.

J Exp Clin Cancer Res. 2018-9-12

[4]
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BMC Neurol. 2017-2-10

[5]
MicroRNA‑301a/ZNRF3/wnt/β‑catenin signal regulatory crosstalk mediates glioma progression.

Int J Oncol. 2021-1

[6]
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Oncol Rep. 2021-7

[7]
Trichosanthin suppresses the proliferation of glioma cells by inhibiting LGR5 expression and the Wnt/β-catenin signaling pathway.

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[8]
Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling.

PLoS One. 2021

[9]
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Eur Rev Med Pharmacol Sci. 2019-5

[10]
IL‑21/IL‑21R inhibit tumor growth and invasion in non‑small cell lung cancer cells via suppressing Wnt/β‑catenin signaling and PD‑L1 expression.

Int J Mol Med. 2019-9-26

本文引用的文献

[1]
CUX1 Facilitates the Development of Oncogenic Properties Activating Wnt/β-Catenin Signaling Pathway in Glioma.

Front Mol Biosci. 2021-8-6

[2]
N-cadherin upregulation mediates adaptive radioresistance in glioblastoma.

J Clin Invest. 2021-3-15

[3]
Sevoflurane Limits Glioma Progression by Regulating Cell Proliferation, Apoptosis, Migration, and Invasion via miR-218-5p/DEK/β-Catenin Axis in Glioma.

Cancer Manag Res. 2021-2-26

[4]
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Front Bioeng Biotechnol. 2020-12-7

[5]
E2F1-mediated repression of WNT5A expression promotes brain metastasis dependent on the ERK1/2 pathway in EGFR-mutant non-small cell lung cancer.

Cell Mol Life Sci. 2021-3

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β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion.

J Exp Med. 2020-11-2

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Neuro Oncol. 2021-1-30

[8]
FDPS promotes glioma growth and macrophage recruitment by regulating CCL20 via Wnt/β-catenin signalling pathway.

J Cell Mol Med. 2020-8

[9]
Radiation resistance of normal human astrocytes: the role of non-homologous end joining DNA repair activity.

J Radiat Res. 2019-1-1

[10]
Infiltrative and drug-resistant slow-cycling cells support metabolic heterogeneity in glioblastoma.

EMBO J. 2018-10-15

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