Ding Rumeng, Kan Quancheng, Wang Ting, Xiao Ran, Song Yanan, Li Duolu
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Front Pharmacol. 2025 Jan 8;15:1483896. doi: 10.3389/fphar.2024.1483896. eCollection 2024.
Triple-negative breast cancer (TNBC) is the most challenging subtype of breast cancer to treat. While previous studies have demonstrated that ginsenoside Rh2 induces apoptosis in TNBC cells, the specific molecular targets and underlying mechanisms remain poorly understood. This study aims to uncover the molecular mechanisms through which ginsenoside Rh2 regulates apoptosis and proliferation in TNBC, offering new insights into its therapeutic potential.
Network analysis and transcriptome sequencing were utilized to explore the potential mechanisms of ginsenoside Rh2 in treating TNBC. imaging and immunohistochemistry were employed to examine the effects of ginsenoside Rh2 in a TNBC mouse model. Functional assays were conducted to assess the impact of ginsenoside Rh2 on TNBC cell behavior. Additionally, ELISA, Western blot, and quantitative real-time PCR were used to further investigate the mechanisms of ginsenoside Rh2-induced apoptosis in TNBC cells.
Through network analysis, 47 common targets were identified, and Gene Ontology (GO) enrichment analysis suggested that ginsenoside Rh2 may exert therapeutic effects in TNBC by influencing apoptosis, cell proliferation, and protein kinase activity. Both transcriptomic analysis and network analysis revealed the JAK/STAT signaling pathway as a key mechanism. Ginsenoside Rh2 inhibited tumor growth in TNBC mice and reduced the expression of IL- 6, IL-6R, STAT3, Bcl-2, and Bcl-xL in tumor tissues. The ability of ginsenoside Rh2 to inhibit TNBC cell proliferation was further confirmed by attenuating the activation of the IL-6/JAK2/STAT3 apoptosis pathway and reducing the expression of protein kinases AMPK-α1 and PKA-Cα.
Based on network analysis and experimental validation, our findings demonstrate that ginsenoside Rh2 regulates TNBC proliferation and apoptosis through suppression of the IL-6/JAK2/STAT3 pathway, both and . This comprehensive approach represents a significant advancement in understanding the therapeutic potential of ginsenoside Rh2 in treating TNBC.
三阴性乳腺癌（TNBC）是最难治疗的乳腺癌亚型。虽然先前的研究表明人参皂苷Rh2可诱导TNBC细胞凋亡，但其具体分子靶点和潜在机制仍知之甚少。本研究旨在揭示人参皂苷Rh2调节TNBC细胞凋亡和增殖的分子机制，为其治疗潜力提供新的见解。
利用网络分析和转录组测序探索人参皂苷Rh2治疗TNBC的潜在机制。采用成像和免疫组织化学方法检测人参皂苷Rh2在TNBC小鼠模型中的作用。进行功能实验以评估人参皂苷Rh2对TNBC细胞行为的影响。此外，采用酶联免疫吸附测定（ELISA）、蛋白质印迹法（Western blot）和定量实时聚合酶链反应（qRT-PCR）进一步研究人参皂苷Rh2诱导TNBC细胞凋亡的机制。
通过网络分析，确定了47个共同靶点，基因本体（GO）富集分析表明人参皂苷Rh2可能通过影响细胞凋亡、细胞增殖和蛋白激酶活性在TNBC中发挥治疗作用。转录组分析和网络分析均显示Janus激酶/信号转导和转录激活因子（JAK/STAT）信号通路是关键机制。人参皂苷Rh2抑制TNBC小鼠肿瘤生长，并降低肿瘤组织中白细胞介素-6（IL-6）、IL-6受体（IL-6R）、信号转导和转录激活因子3（STAT3）、B细胞淋巴瘤-2（Bcl-2）和Bcl-xL的表达。通过减弱IL-6/Janus激酶2（JAK2）/STAT3凋亡途径的激活并降低蛋白激酶5′-腺苷酸激活蛋白激酶α1（AMPK-α1）和蛋白激酶A催化亚基α（PKA-Cα）的表达，进一步证实了人参皂苷Rh2抑制TNBC细胞增殖的能力。
基于网络分析和实验验证，我们的研究结果表明人参皂苷Rh2通过抑制IL-6/JAK2/STAT3途径调节TNBC的增殖和凋亡。这种综合方法代表了在理解人参皂苷Rh2治疗TNBC的治疗潜力方面的重大进展。
