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为探究山竹醇抗乳腺癌的作用机制及对上皮细胞亚群的靶向关联特征，通过网络药理学筛选山竹醇潜在靶点283个及乳腺癌相关靶点4560个，获得两者交集靶点192个，构建PPI网络并筛选出TP53、SRC、AKT1等核心靶点；GO/KEGG富集分析显示潜在靶点主要集中于癌症通路、MAPK信号通路等肿瘤相关通路.分子对接验证山竹醇与潜在靶点具有良好结合活性（结合能≤-5.0kcal/mol），其中与STAT3的结合能-8.7 kcal/mol.细胞实验表明：山竹醇浓度依赖性抑制两株乳腺癌细胞增殖，下调mRNA转录及翻译后修饰（p-STAT3、p-AKT和p-SRC）.单细胞测序分析明确了MCF-7和MDA-MB-231细胞的亚群组成，筛选出关键上皮细胞亚群，其潜在靶向通路与网络药理学预测的通路高度匹配.交集分析发现山竹醇调控MCF-7（增殖-凋亡）和MDA-MB-231（侵袭-迁移）恶性表型的潜在基因与通路.研究揭示了山竹醇抗乳腺癌的特异性调控机制，为乳腺癌个体化治疗及山竹醇的临床转化提供了理论依据.
Abstract：To investigate the mechanism of action of garcinol against breast cancer and the characteristics of targeted association with epithelial cell subsets, 283 potential targets of garcinol and 4560 targets related to breast cancer were screened by network pharmacology, 192 intersection targets were obtained, PPI network was constructed and core targets such as TP53, SRC, and AKT1 were selected; GO/KEGG enrichment analysis showed that potential targets were mainly concentrated in tumor-related pathways such as pathway signaling in cancer and MAPK pathway. Molecular docking verified that garcinol had good binding activity(binding energy≤-5.0 kcal/mol) to potential targets, with binding energy-8.7 kcal/mol to STAT3. Cell experiments showed that garcinol concentration-dependently inhibited the proliferation of two breast cancer cells and down-regulated mRNA transcription and post-translational modifications(p-STAT3, p-AKT and p-SRC). Single-cell sequencing analysis identified the subset composition of MCF-7 and MDA-MB-231 cells and selected key epithelial cell subsets whose potential targeted pathways closely matched those predicted by network pharmacology. Intersection analysis revealed potential genes and pathways involved in the regulation of malignant phenotypes of MCF-7(proliferation-apoptosis) and MDA-MB-231(invasion-migration) by garcinol. The study reveals the specific regulatory mechanism of garcinol against breast cancer and provides a theoretical basis for individualized treatment of breast cancer and clinical translation of garcinol.
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基本信息:
DOI：10.20056/j.cnki.ZNMDZK.20260754
中图分类号:R965
引用信息:
[1]张文龙,刘金虹,姚慧,等.网络药理学及单细胞测序技术对山竹醇抗乳腺癌潜在通路及上皮细胞亚群关联分析[J].中南民族大学学报(自然科学版)().DOI:10.20056/j.cnki.ZNMDZK.20260754.
基金信息:
国家自然科学基金资助项目(81201610); 湖北省自然科学基金资助项目(2023AFB681); 中央高校基本科研业务费专项资金资助项目(CZY17014)
2026-06-24
2026-06-24
2026-06-24