背景:肝细胞癌(HCC),一种全球常见的癌症,经常表现得很晚,对化疗表现出很高的抵抗力,导致治疗效果欠佳。传统中药成分因其抗癌特性而被认可。
目的:探讨五味子木脂素和叶黄素通过细胞外信号调节激酶(ERK)1/2通路抑制肝癌细胞上皮-间质转化(EMT)的机制,并确定生物标志物,分子亚型,并通过多组学靶向精确肿瘤学。
方法:使用细胞计数试剂盒-8(CCK-8)测定法评估增殖,用划痕和transwell测定法评估入侵和迁移。流式细胞术定量凋亡率。CCL20、p-ERK1/2、c-Myc、Vimentin,通过实时PCR和Westernblot分析E-cadherin/N-cadherin。用特定的公式计算肿瘤体积,和增长。
结果:五味子木脂素和叶黄素组合降低CCL20表达,抑制肝癌的增殖和迁移,并以剂量和时间依赖性方式增强细胞凋亡。分子分析显示E-cadherin增加和N-cadherin减少,p-ERK1/2,c-Myc,和波形蛋白表达,表明ERK1/2途径调制。在体内,治疗裸鼠显示肿瘤生长和体积显著降低。
结论:五味子木脂素和叶黄素可能抵消CCL20诱导的EMT,入侵,并通过ERK1/2途径在肝癌细胞中迁移,增强细胞凋亡。多组学分析进一步有助于精确确定癌症治疗的新型生物标志物。
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.