Multi-omics analysis reveals mechanism of Schisandra chinensis lignans and acteoside on EMT in hepatoma cells via ERK1/2 pathway

被引:1
作者
Jiang, Jingjing [1 ]
Cheng, Ru [1 ]
Song, Aoqi [1 ]
Lou, Yuefen [1 ]
Fan, Guorong [2 ]
机构
[1] Tongji Univ, Shanghai Peoples Hosp 4, Sch Med, Dept Pharm, Shanghai 200434, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Clin Pharm, Shanghai 200080, Peoples R China
关键词
Schisandra chinensis lignans; Acteoside; Liver cancer; Epithelial-mesenchymal transition; Extracellular regulated kinases 1/2 pathway; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA; CCL20; EXPRESSION; MIGRATION; CANCER; PROLIFERATION; PROGRESSION;
D O I
10.1007/s10142-024-01351-w
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
BackgroundHepatocellular 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.ObjectiveExploring 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.MethodsProliferation 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.ResultsThe 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.ConclusionSchisandra 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.
引用
收藏
页数:11
相关论文
共 30 条
[1]   Brusatol reverses lipopolysaccharide-induced epithelial-mesenchymal transformation and induces apoptosis through PI3K/Akt/NF-κB pathway in human gastric cancer SGC-7901 cells [J].
Chen, Hejuntao ;
Jiang, Ting ;
Chen, Hui ;
Su, Jingjing ;
Wang, Xuncui ;
Cao, Yin ;
Li, Qinglin .
ANTI-CANCER DRUGS, 2021, 32 (04) :394-404
[2]   Selective Recruitment of Regulatory T Cell through CCR6-CCL20 in Hepatocellular Carcinoma Fosters Tumor Progression and Predicts Poor Prognosis [J].
Chen, Kang-Jie ;
Lin, Sheng-Zhang ;
Zhou, Lin ;
Xie, Hai-Yang ;
Zhou, Wu-Hua ;
Taki-Eldin, Ahmed ;
Zheng, Shu-Sen .
PLOS ONE, 2011, 6 (09)
[3]   CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition [J].
Cheng, Xian-Shuo ;
Li, Yun-Feng ;
Tan, Jing ;
Sun, Bin ;
Xiao, You-Chuan ;
Fang, Xing-Bao ;
Zhang, Xiao-Feng ;
Li, Qiang ;
Dong, Jian-Hua ;
Li, Ming ;
Qian, Hai-hua ;
Yin, Zheng-Feng ;
Yang, Zhi-Bin .
CANCER LETTERS, 2014, 348 (1-2) :77-87
[4]   Wound healing and anti-inflammatory activities induced by a Plantago australis hydroethanolic extract standardized in verbascoside [J].
de Moura Sperotto, Nathalia Denise ;
Steffens, Luiza ;
Verissimo, Rodrigo Moises ;
Henn, Jeferson Gustavo ;
Peres, Valeria Flores ;
Vianna, Priscila ;
Bogo Chies, Jose Artur ;
Roehe, Adriana ;
Saffi, Jenifer ;
Moura, Dinara Jaqueline .
JOURNAL OF ETHNOPHARMACOLOGY, 2018, 225 :178-188
[5]   High Expression of CCL20 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma after Curative Resection [J].
Ding, Xiangjiu ;
Wang, Kexin ;
Wang, Hui ;
Zhang, Guangyong ;
Liu, Yajing ;
Yang, Qingyun ;
Chen, Weijie ;
Hu, Sanyuan .
JOURNAL OF GASTROINTESTINAL SURGERY, 2012, 16 (04) :828-836
[6]  
European Assoc Study Liver, 2012, EUR J CANCER, V48, P599, DOI [10.1016/j.ejca.2011.12.021, 10.1016/j.jhep.2011.12.001]
[7]   Hepatocellular carcinoma [J].
Forner, Alejandro ;
Reig, Maria ;
Bruix, Jordi .
LANCET, 2018, 391 (10127) :1301-1314
[8]   Inflammatory mechanism of cerebral ischemia-reperfusion injury with treatment of stepharine in rats [J].
Hao, Tingyu ;
Yang, Yanqiu ;
Li, Ning ;
Mi, Yan ;
Zhang, Guijie ;
Song, Junyu ;
Liang, Yusheng ;
Xiao, Jiao ;
Zhou, Di ;
He, Dakuo ;
Hou, Yue .
PHYTOMEDICINE, 2020, 79
[9]   Chemokine ligand 20 enhances progression of hepatocellular carcinoma via epithelial-mesenchymal transition [J].
Hou, Ke-Zhu ;
Fu, Zhi-Qiang ;
Gong, Hua .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (02) :475-483
[10]   Over-expression of regulator of G protein signaling 5 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells [J].
Hu, Minghua ;
Chen, Xiaobing ;
Zhang, Jianmin ;
Wang, Dong ;
Fang, Xiaosan ;
Wang, Xiaoming ;
Wang, Guannan ;
Chen, Guoyong ;
Jiang, Xiaochun ;
Xia, Hongping ;
Wang, Yongsheng .
JOURNAL OF SURGICAL ONCOLOGY, 2013, 108 (03) :192-196