Bavachinin Suppresses Growth and Metastasis of Oral Squamous Cell Carcinoma through GSK-3β/β-Catenin Pathway: Potential for Synergistic Anticancer Therapy with Cisplatin.

IF 6.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal Pub Date : 2026-04-07 DOI:10.1016/j.bj.2026.100975

Pei-Yu Hsu, Yann-Lii Leu, Chin-Chuan Chen, Min Chen, Kai-Ping Chang, Wan-Ling Wang, Fei-Wen Jan, Sien-Hung Yang, Chia-Yu Yang

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引用次数: 0

Abstract

Background: Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis, often complicated by recurrence, metastasis, and chemoresistance. While cisplatin remains a cornerstone of OSCC treatment, its efficacy is limited by systemic toxicity and resistance. In search of safer, effective adjunctive strategies, we investigated bavachinin, a flavanone from Psoralea corylifolia L., for its antitumor potential in OSCC.

Materials and methods: Integrated in vitro, in silico, and in vivo approaches were employed. Functional assays evaluated cell viability, apoptosis, migration, and invasion. Transcriptomic profiling identified dysregulated pathways, with key targets validated by quantitative reverse transcription PCR (qRT-PCR). Molecular docking predicted protein targets, confirmed by Western blot. Toxicity and therapeutic efficacy were evaluated in C57BL/6 mice and OSCC cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.

Results: Bavachinin significantly reduced cell viability, induced G2/M phase arrest, promoted apoptosis, and inhibited migration and invasion in OSCC cells. Transcriptomic profiling and qRT-PCR revealed suppression of genes involved in extracellular matrix remodeling and cell adhesion. Glycogen synthase kinase-3β (GSK-3β) was identified as a potential target by molecular docking analysis, confirmed by increased phosphorylation at Tyr216 and β-catenin degradation, leading to downregulation of matrix metalloproteinase-2 and fibronectin. As natural compounds are rarely used as monotherapies, bavachinin combined with cisplatin showed synergistic antitumor effects in OSCC CDX and PDX models, without systemic toxicity in mice.

Conclusion: Bavachinin exerts potent antitumor effects via modulation of the GSK-3β/β-catenin pathway and may serve as a promising adjunct to cisplatin in OSCC treatment.

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巴伐利亚蛋白通过GSK-3β/β-Catenin途径抑制口腔鳞状细胞癌的生长和转移：与顺铂协同抗癌治疗的潜力

背景：口腔鳞状细胞癌（OSCC）是一种高度侵袭性的恶性肿瘤，预后较差，常伴有复发、转移和化疗耐药。虽然顺铂仍然是OSCC治疗的基石，但其疗效受到全身毒性和耐药性的限制。为了寻找更安全、有效的辅助治疗策略，我们研究了骨补骨脂黄酮巴伐利亚素在OSCC中的抗肿瘤潜力。材料和方法：采用体外、计算机和体内相结合的方法。功能试验评估细胞活力、凋亡、迁移和侵袭。转录组学分析鉴定了失调的途径，并通过定量反转录PCR （qRT-PCR）验证了关键靶点。分子对接预测蛋白靶点，经Western blot证实。在C57BL/6小鼠和OSCC细胞系来源的异种移植物（CDX）和患者来源的异种移植物（PDX）模型中评估毒性和治疗效果。结果：巴伐青素显著降低细胞活力，诱导G2/M期阻滞，促进细胞凋亡，抑制细胞迁移和侵袭。转录组学分析和qRT-PCR显示参与细胞外基质重塑和细胞粘附的基因受到抑制。糖原合成酶激酶-3β (GSK-3β)通过分子对接分析被确定为潜在靶点，通过Tyr216位点磷酸化增加和β-catenin降解，导致基质金属蛋白酶-2和纤维连接蛋白下调证实。由于天然化合物很少作为单一疗法使用，巴伐丁素联合顺铂在OSCC CDX和PDX模型中显示协同抗肿瘤作用，对小鼠无全身毒性。结论：巴伐利亚蛋白通过调节GSK-3β/β-catenin通路发挥有效的抗肿瘤作用，可能作为顺铂治疗OSCC的一种有前景的辅助药物。

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

Biomedical Journal Medicine-General Medicine

CiteScore

11.60

自引率

1.80%

发文量

128

审稿时长

42 days

期刊介绍： Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs. Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology. A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.