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高良姜通过上调三阴性乳腺癌中促凋亡基因BAX来促进细胞凋亡。

Galangin promotes apoptosis by upregulating the pro-apoptotic gene BAX in triple-negative breast cancer.

作者信息

Sinnarkar Shruti, Suryawanshi Poonam, Dilip Amol, Bhawalkar Jitendra, Ladke Vaibhav

机构信息

Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, India.

Central Research Facility, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, (Deemed to Be University), Sant Tukaram Nagar, Pimpri, Pune, 411018, India.

出版信息

J Egypt Natl Canc Inst. 2024 Dec 20;36(1):41. doi: 10.1186/s43046-024-00246-y.

DOI:10.1186/s43046-024-00246-y
PMID:39702881
Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is one of the most aggressive and formidable subtypes of breast cancer, devoid of targeted therapy and frequently leading to unfavorable prognoses and significant side effects. The demand for creative and effective treatment options has prompted the current study to investigate the potential of natural chemicals as therapeutic agents. This study intends to examine the efficacy of Galangin, a naturally occurring flavonoid, in treating triple-negative breast cancer.

METHODS

The research utilizes a dual methodology, combining in silico network pharmacology with in vitro experimental methods. The in silico research proved crucial in finding significant gene targets and cellular signaling pathways influenced by Galangin in triple-negative breast cancer. To corroborate these computational predictions, a variety of in vitro studies were conducted, including the MTT assay, wound scratch assay, apoptosis assay, reactive oxygen species assay, mitochondrial membrane potential assessment, and RT-PCR.

RESULTS

Fifteen prevalent genes were identified, demonstrating involvement in cellular proliferation, apoptosis regulation, cell migration, MAPK cascade regulation, and cell cycle regulation. The predominant genes implicated in the ten principal pathways were MAPK1, MAPK8, MAPK14, and IL6, which were observed to be linked to the MAPK signaling pathway, perhaps serving as the critical channel through which Galangin may facilitate the treatment of oral cancer. In vitro experiments demonstrated anti-proliferative effects, late-stage apoptosis, anti-migratory characteristics, antioxidant activity, and upregulation of the pro-apoptotic BAX gene.

CONCLUSION

This study's results demonstrate that Galangin possesses considerable anti-proliferative effects on TNBC cells, underscoring its potential as a viable therapeutic drug. These findings facilitate the development of more effective and precisely focused therapy approaches for TNBC, providing optimism for enhanced treatment outcomes for patients suffering from this challenging disease.

摘要

背景

三阴性乳腺癌(TNBC)是最具侵袭性和棘手的乳腺癌亚型之一,缺乏靶向治疗方法,且常常导致不良预后和严重的副作用。对创新且有效的治疗方案的需求促使本研究去探究天然化学物质作为治疗药物的潜力。本研究旨在考察高良姜素(一种天然存在的类黄酮)治疗三阴性乳腺癌的疗效。

方法

本研究采用双重方法,将计算机网络药理学与体外实验方法相结合。计算机研究对于发现受高良姜素影响的三阴性乳腺癌中的重要基因靶点和细胞信号通路至关重要。为了证实这些计算预测结果,进行了多种体外研究,包括MTT法、划痕实验、凋亡检测、活性氧检测、线粒体膜电位评估以及逆转录聚合酶链反应(RT-PCR)。

结果

鉴定出15个常见基因,这些基因参与细胞增殖、凋亡调控、细胞迁移、丝裂原活化蛋白激酶(MAPK)级联调控和细胞周期调控。在十条主要通路中涉及的主要基因是MAPK1、MAPK8、MAPK14和IL6,观察到它们与MAPK信号通路相关联,这可能是高良姜素促进口腔癌治疗的关键途径。体外实验证明了其具有抗增殖作用、晚期凋亡作用、抗迁移特性、抗氧化活性以及促凋亡BAX基因的上调。

结论

本研究结果表明,高良姜素对三阴性乳腺癌细胞具有显著的抗增殖作用,突显了其作为一种可行治疗药物的潜力。这些发现有助于开发更有效且针对性更强的三阴性乳腺癌治疗方法,为患有这种具有挑战性疾病的患者改善治疗效果带来了希望。

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