Department of Pharmacy, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
Funct Integr Genomics. 2024 Jun 8;24(3):112. doi: 10.1007/s10142-024-01351-w.
Hepatocellular carcinoma (HCC), a globally common cancer, often presents late and shows high resistance to chemotherapy, resulting in suboptimal treatment efficacy. Components from traditional Chinese medicines have been recognized for their anti-cancer properties.
Exploring the mechanism of Schisandra chinensis lignans and acteoside in suppressing Epithelial-Mesenchymal Transition (EMT) in hepatoma cells through the Extracellular signal-Regulated Kinases (ERK)1/2 pathway and identifying biomarkers, molecular subtypes, and targets via multi-omics for precision oncology.
Proliferation was assessed using cell counting kit-8 (CCK-8) assays, with scratch and transwell assays for evaluating invasion and migration. Flow cytometry quantified apoptosis rates. Expression levels of CCL20, p-ERK1/2, c-Myc, Vimentin, and E-cadherin/N-cadherin were analyzed by real-time PCR and Western blot. Tumor volume was calculated with a specific formula, and growth.
The Schisandra chinensis lignans and acteoside combination decreased CCL20 expression, inhibited hepatoma proliferation and migration, and enhanced apoptosis in a dose- and time-dependent manner. Molecular analysis revealed increased E-cadherin and decreased N-cadherin, p-ERK1/2, c-Myc, and Vimentin expression, indicating ERK1/2 pathway modulation. In vivo, treated nude mice showed significantly reduced tumor growth and volume.
Schisandra chinensis lignans and acteoside potentially counteract CCL20-induced EMT, invasion, and migration in hepatocellular carcinoma cells via the ERK1/2 pathway, enhancing apoptosis. Multi-omics analysis further aids in pinpointing novel biomarkers for precision cancer therapy.
肝细胞癌（HCC）是一种全球常见的癌症，通常发现较晚，对化疗具有较高的耐药性，导致治疗效果不佳。中药成分已被证实具有抗癌特性。
通过细胞外信号调节激酶（ERK）1/2 通路探讨五味子木脂素和獐牙菜苦苷抑制肝癌细胞上皮-间充质转化（EMT）的作用机制，并通过多组学鉴定生物标志物、分子亚型和靶点，实现精准肿瘤学。
使用细胞计数试剂盒-8（CCK-8）检测细胞增殖，划痕和 Transwell 检测评估侵袭和迁移。流式细胞术定量细胞凋亡率。实时 PCR 和 Western blot 分析 CCL20、p-ERK1/2、c-Myc、波形蛋白和 E-钙黏蛋白/N-钙黏蛋白的表达水平。采用特定公式计算肿瘤体积并观察生长情况。
五味子木脂素和獐牙菜苦苷联合用药呈剂量和时间依赖性地降低 CCL20 表达，抑制肝癌细胞增殖、迁移，并增强细胞凋亡。分子分析显示 E-钙黏蛋白表达增加，N-钙黏蛋白、p-ERK1/2、c-Myc 和波形蛋白表达减少，提示 ERK1/2 通路的调节。体内实验中，经处理的裸鼠肿瘤生长和体积明显减小。
五味子木脂素和獐牙菜苦苷可能通过 ERK1/2 通路拮抗 CCL20 诱导的 HCC 细胞 EMT、侵袭和迁移，增强细胞凋亡。多组学分析进一步有助于确定精准肿瘤治疗的新型生物标志物。
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