2-Methoxy-4-vinylphenol mitigates malignancy of cholangiocarcinoma cells through the blockade of sonic hedgehog signalling

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical and biophysical research communications Pub Date : 2025-03-25 Epub Date: 2025-02-21 DOI:10.1016/j.bbrc.2025.151515

Jungwhoi Lee , Nur Azizah Arryanie Binti Morshidi , Jungsul Lee , Woogwang Sim , Jae-Hoon Kim

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Abstract

Background

Cholangiocarcinoma (CCA) is one of the most refractory malignancies with a grave prognosis. 2-Methoxy-4-vinylpenol (2M4VP) is a well-known flavonoid having beneficial functions in human health including an anti-cancer effect in various malignant tumours. However, the anti-cancer effect of 2M4VP against CCA remains ambiguous.

Purpose

The present study aimed to investigate the bio-activity of 2M4VP in human CCA.

Methods

Biological activities of 2M4VP were examined using in vitro assays. Prognostic values were assessed using Kaplan-Meier and Liptak's z score analyses.

Results

2M4VP significantly attenuated the anti-migratory features of CCA cells when compared to human intrahepatic bile duct epithelial cells (HIBEpiC), but not in viability. The anti-cancer effect of 2M4VP was induced by down-regulating the expression of cellular sonic hedgehog (Shh) signalling molecule such as GLI family zinc finger 3 (GLI3). In addition, 2M4VP treatment evoked a synergic anti-cancer effect when used in combination with gemcitabine. Furthermore, high GLI3 expression was significantly associated with a poor prognosis in patients with CCA.

Conclusions

These results collectively indicate that 2M4VP might be a natural reagent against CCA metastasis, functioning through the ablating Shh signalling associated GLI3 expression, which provides the rationale for further investigation and a potential clinical trial using 2M4VP against CCA.

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2-甲氧基-4-乙烯基酚通过阻断超音hedgehog信号通路减轻胆管癌细胞的恶性肿瘤

背景胆管癌（CCA）是最难治性的恶性肿瘤之一，预后严重。2-甲氧基-4-乙烯基苯酚（2M4VP）是一种众所周知的类黄酮，对人体健康具有有益的功能，包括对各种恶性肿瘤的抗癌作用。然而，2M4VP对CCA的抗癌作用尚不明确。目的研究2M4VP在人CCA中的生物活性。方法采用体外法检测2M4VP的生物活性。采用Kaplan-Meier和Liptak’s z评分分析评估预后价值。结果与人肝内胆管上皮细胞（HIBEpiC）相比，2m4vp显著降低CCA细胞的抗迁移特性，但不影响其活力。2M4VP的抗癌作用是通过下调GLI家族锌指3 （GLI3）等细胞Shh信号分子的表达而诱导的。此外，2M4VP治疗与吉西他滨联合使用时可产生协同抗癌作用。此外，高GLI3表达与CCA患者的不良预后显著相关。结论这些结果表明，2M4VP可能是一种天然的抗CCA转移试剂，通过消融Shh信号相关的GLI3表达发挥作用，这为进一步研究和使用2M4VP抗CCA的潜在临床试验提供了依据。

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

Biochemical and biophysical research communications 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

1400

审稿时长

14 days

期刊介绍： Biochemical and Biophysical Research Communications is the premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research. The development of the "Breakthroughs and Views" section brings the minireview format to the journal, and issues often contain collections of special interest manuscripts. BBRC is published weekly (52 issues/year).Research Areas now include: Biochemistry; biophysics; cell biology; developmental biology; immunology ; molecular biology; neurobiology; plant biology and proteomics